Fatty Acids for the Treatment of Crohn's Disease

Omega-3 Fatty Acids

A Japanese epidemiological study found a correlation between high omega-6:omega-3 fatty acid (FA) ratios and incidence of Crohn's Disease.²¹² In patients with diagnosed Crohn's Disease, eicosapentaenoic acid (EPA) and total polyunsaturated fatty acids were significantly decreased, while the ratio of omega- 6:omega-3 FA was increased compared to controls. There was also a negative correlation between EPA levels and disease activity, with lower levels observed in active disease compared to disease remission. ²³⁸

High omega-6:omega-3 FA ratios can contribute to inflammation. The omega-6 linoleic acid has been found in vitro to enhance arachidonic acid-induced inflammatory cytokine production in intestinal tissue from Crohns Disease patients.²³⁹ On the other hand, the anti-inflammatory effects of omega-3 fish oils have been well established. Thus, increasing the intake of omega-3 fatty acids in the diet or by supplementation seems prudent. Table 8 summarizes intervention trials of omega-3 fatty acids for Crohn's Disease.

Elemental diets used in enteral nutrition often consist of only small amounts of fat in the form of soy oil, which can result in a deficiency of essential fatty acids (EFAs). A Japanese study examined the effect of a special Crohn’s disease diet (CDD) enriched with omega-3 fatty acids in a ratio of 0.5 omega-3:omega-6 FA that also included a simple orally-ingested diet of rice gruel, progressing to steamed rice and small amounts of meat and noodles. Patients used the elemental diet for breakfast and dinner and the Crohn’s disease diet for lunch, and were gradually weaned off the elemental diet as their disease activity permitted. Use of the omega-3 enriched diet resulted in a decrease in CRP, a measurement of inflammation.²⁴⁰

A study examined the anti-inflammatory effects of omega-3 fatty acids from fish oil on 39 IBD patients (29 with Crohns Disease). In this double-blind, crossover trial, patients were given either a fish oil supplement containing 1.8 g EPA and 1.3 g docosahexaenoic acid (DHA) daily or an olive oil placebo for three months. After a one-month washout period they were switched to the other protocol. Clinical disease activity was determined by the CDAI and endoscopy at the end of each phase. Laboratory evaluation consisted of determination of fatty acid composition of biopsy specimens, urinary excretion of the inflammatory mediator thromboxane B2 (TxB2), and plasma leukotriene B4 (LTB4) levels. Levels of TxB2 and LTB4 decreased by one-third in patients taking omega-3 supplementation. Endoscopy revealed a small morphological improvement in 13 Crohn's Disease patients on fish oil compared to placebo. On biopsy exam, EPA content of phospholipids from colonic mucosa increased three-fold with fish oil supplementation, whereas DHA increased only slightly. During the control period arachidonic acid levels were significantly higher in inflamed than non-inflamed gut mucosa. These differences diminished during fish oil supplementation. No significant difference in disease activity between fish oil and placebo was noted in the Crohns Disease patients (unlike the Ulcerative Colitis patients in the study). Thus, although the fish oil seemed to have anti-inflammatory effects, they were not enough to contribute to decreased disease activity in Crohn's Disease.²⁴¹

Another study examined incorporation of fatty acids into the colonic mucosa of IBD patients. Similar to the foregoing study, supplementation of fish oil (18 g daily) resulted in significantly increased incorporation of EPA (seven-fold) and DHA (1.5-fold) into gut mucosa and decreased inflammatory eicosanoid production, compared to olive oil that did not suppress eicosanoid production. ²⁴²

Two treatment protocols were compared against a placebo in 204 Crohns Disease patients in remission (CDAI 150) 5 g concentrated fish oil daily, low carbohydrate diet (84 g daily), or placebo consisting of 5 g corn oil daily. There was no significant difference between fish oil and placebo groups regarding percent of patients experiencing relapse within one year. Corn oil, a source of linoleic acid, could have provided antiinflammatory effects via conversion to gammalinolenic acid (GLA) and ultimately the antiinflammatory prostaglandin-1 series, thus confounding the results. The low carbohydrate diet provided significant benefit.²⁴³

A study published in the New England Journal of Medicine examined the effect of enteric- coated (to resist gastric acid for 30 minutes but to allow disintegration by 60 minutes) fish oil capsules for the prevention of relapse in Crohns Disease. Seventy- eight patients were randomly assigned to receive three 500-mg fish oil capsules three times daily or placebo. Fish oil capsules contained 40- percent EPA, 20-percent DHA, and a 40-percent mixture of fatty acids, for a total daily dose of 1.8 g EPA and 0.9 g DHA. Placebo consisted of 60- percent caprylic acid and 40-percent capric acid. Requirements for admission in the study included remission for at least three months (defined as a CDAI score 150) but less than two years and avoidance of conventional medications for at least three months. Thirty-four of 39 patients in the fishoil group and 37/39 in the placebo group completed the one-year study. Eleven patients in the fish oil group (32%) experienced relapses compared to 27 patients in the placebo group (73%). The authors speculate the improvement with fishoil capsules may be attributed to anti-inflammatory effects of omega-3 fatty acids, including inhibition of leukotrienes, thromboxanes, and TNFalpha. ²⁴⁴

A pilot study examined the effect of seal oil instilled into the duodenum in five patients with Crohn's Disease and five with Ulcerative Colitis. Seal oil (10 mL) was administered three times daily directly into a nasoduodenal feeding tube. Seal oil provided 1.8 g EPA, 2.6 g DHA, and 1.0 g docosapentaenoic acid (DPA; an omega-3 fatty acid not found in fish oil that affects other anti-inflammatory pathways). According to the researchers, the omega-3 FAs from seal oil are more easily hydrolyzed to free fatty acids than those from fish oil. Treatment for 10 days resulted in significant decreases in disease activity and IBD-associated joint pain, and increases in omega-3:omega-6 ratios in mucosal tissue and blood.²⁴⁵

Short-chain Fatty Acids

Short-chain fatty acids, such as butyric acid, provide the main fuel for colonocytes and have been examined in the form of enemas for UC. Butyric acid may also provide benefit for Crohn's Disease. Intestinal biopsies from Crohn's Disease patients were examined with and without exposure to butyric acid. The researchers found butyric acid resulted in decreased NF-kappaB-stimulated TNF-alpha, providing a mechanism for its potential use in Crohn's Disease.²⁴⁶



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