Diet as a treatment for inflammatory bowel disease: is it ready for prime time?

PURPOSE OF REVIEW: Diet remains an important topic for patients with inflammatory bowel disease (IBD), yet few guidelines for dietary recommendations exist. There is a growing interest in the use of diet as treatment or adjuvant therapy for both ulcerative colitis and Crohn's disease. Here, we highlight the latest evidence on the use of diet for treatment of symptoms, active disease and maintenance of remission in ulcerative colitis and Crohn's disease. RECENT FINDINGS: The Crohn's Disease Exclusion Diet (CDED) and the Specific Carbohydrate Diet (SCD) are studied diets that have gained popularity, but there is growing interest in the use and efficacy of less restrictive diets such as the Mediterranean diet. Recent data suggest healthful dietary patterns alone, with an emphasis on whole foods that are high in vegetable fibre and that promote less consumption of ultra-processed foods may also help achieve remission in patients with ulcerative colitis and Crohn's disease. SUMMARY: In this review, we summarize the literature on diet as treatment for IBD. We highlight the latest clinical dietary studies, randomized clinical trials, as well as new and emerging diets for the treatment of IBD.

Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney.

BACKGROUND/AIMS: Carnitine is essential for the transport of long-chain FAs (FA) into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. METHODS: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH), organic cation transporter (OCTN2), and peroxisome proliferator-activated receptor (PPARα), a regulator of fatty acid oxidation activated by FAs. RESULTS: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. CONCLUSIONS: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

The role of intrahepatic CD3+/CD4-/CD8- double negative T (DN T) cells in enhanced acetaminophen toxicity.

UNLABELLED: The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB -/-) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB -/-) mice. Analysis revealed that GrB -/- mice had an increased population of intrahepatic CD3 (+), CD4 (-), and CD8 (-) lymphocytes expressing the CD69 activation marker and Fas ligand. Depletion of these cells in the GrB -/- and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB -/- IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. CONCLUSIONS: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (-), CD8 (-), NK1.1 (-) T cells. Depletion of these cells from GrB -/- mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery.

Shoulder Pain Associated With Multiple Arteriovenous Malformations Successfully Treated With Embolization.

A 44-year-old male presented with left upper extremity and shoulder pain with worsening functional impairment after years of repetitive use, overtraining, and multiple injuries from weightlifting and mixed martial arts. Imaging showed no obvious injury or ligamentous deformity other than mild osteoarthritis (OA) of the left glenohumeral joint. Duplex ultrasonography (US) revealed four arteriovenous malformations (AVMs) surrounding the shoulder joint and left upper extremity. The vasculature was mapped via angiography through a transradial approach. Initial treatment included transarterial embolization of two AVMs off the axillary artery and branching anterior circumflex humeral artery. Secondary treatment included embolization of two lesions months later via direct puncture, one through a transvenous approach and the second through direct transmalformation cannulation, via the nidus, near the clavicle and posterior scapular lateral border. Treatment resulted in significant improvement in pain and range of motion. Follow-up assessments revealed improvement in overall symptoms, recovered function, and return to exercise and competitive mixed martial arts. This case highlights the value of duplex ultrasonography, embolization, and transarterial and transvenous approaches for the treatment of AVM-associated extremity or joint pain.

Embolization for the treatment of large, complex fibroids in an outpatient setting: A report of 2 cases.

Uterine leiomyomas are the most common benign pelvic tumors in premenopausal women, causing significant morbidity. Uterine fibroid embolization is a minimally invasive alternative to traditional open or laparoscopic surgeries for the management of symptomatic uterine leiomyoma. For large fibroids, hospitalization after treatment is often required. However, there are limited data on patients with large, complex uterine leiomyomas treated by embolization. This report of 2 cases describes 2 females with large, complex fibroids causing pain and decreased quality of life who were evaluated and treated with embolization in the outpatient setting. Each patient underwent transradial cannulation and uterine artery embolization under local anesthesia or conscious sedation and returned home without complication. For women wishing to preserve their uterus, uterine fibroid embolization is an effective nonsurgical alternative to hysterectomy and myomectomy in an outpatient setting. If standard protocols are followed, embolization by way of transradial artery catheterization is safe for the treatment of large, complex, symptomatic fibroids in the outpatient setting; however, additional studies with larger cohorts are warranted. Accessing the uterine arteries transradially reduces the risk of intra- and post-operative complications for patients, reduces their time spent in a hospital, and minimizes operating costs.

Biosynthesis of the Essential Fatty Acid Oxidation Cofactor Carnitine Is Stimulated in Heart and Liver after a Single Bout of Exercise in Mice.

We determined whether one single bout of exercise stimulates carnitine biosynthesis and carnitine uptake in liver and heart. Free carnitine (FC) in plasma was assayed using acetyltransferase and [14C]acetyl-CoA in Swiss Webster mice after 1 hour of moderate-intensity treadmill running or 4 hours and 8 hours into recovery. Liver and heart were removed under the same conditions for measurement of carnitine biosynthesis enzymes (liver butyrobetaine hydroxylase, γ-BBH; heart trimethyllysine dioxygenase, TMLD), organic cation transporter-2 (OCTN2, carnitine transporter), and liver peroxisome proliferator-activated receptor-alpha (PPARα, transcription factor for γ-BBH and OCTN2 synthesis). In exercised mice, FC levels in plasma decreased while heart and liver OCTN2 protein expressed increased, reflecting active uptake of FC. During recovery, the rise in FC to control levels was associated with increased liver γ-BBH expression. Protein expression of PPARα was stimulated in liver after exercise and during recovery. Interestingly, heart TMLD protein was also detected after exercise. Acute exercise stimulates carnitine uptake in liver and heart. The rapid return of FC levels in plasma after exercise indicates carnitine biosynthesis by liver is stimulated to establish carnitine homeostasis. Our results suggest that exercise may benefit patients with carnitine deficiency syndromes.

The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury.

UNLABELLED: Patients with cirrhosis have an increased risk of developing liver cancer and a higher rate of mortality. Cirrhosis currently has no known cure, and patients may benefit from new agents aimed at alleviating their complications and slowing down the rate of disease progression. Therefore, the effects of the orally bioavailable synthetic triterpenoid 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-oate-ethyl amide (CDDO-EA, RTA 405), which has potent antioxidative and antiinflammatory properties, was evaluated in a chronic carbon tetrachloride (CCl(4))-induced model of liver cirrhosis and hepatocellular carcinoma (HCC). Mice were injected with CCl(4) (to induce fibrosis and cirrhosis) or placebo biweekly for 12 weeks followed by CDDO-EA in the diet for 18 weeks with continued biweekly injections of CCl(4). Chronic CCl(4) administration resulted in cirrhosis, ascites, and HCC formation, associated with increased serum transforming growth factor-ß1, hepatic hydroxyproline content, and increased serum bilirubin. CDDO-EA, whose administration commenced after establishment of liver fibrosis, decreased liver fibrosis progression, serum bilirubin, ascites, and HCC formation and markedly increased overall survival. CDDO-EA also attenuated -TNFα (tumor necrosis factor-α), α-SMA (alpha smooth muscle actin), augmented -IL-10 levels, and improved histologic and serologic markers of fibrosis. CONCLUSIONS: CDDO-EA mitigates the progression of liver fibrosis induced by chronic CCl(4) administration, which is associated with the induction of antifibrogenic genes and suppression of profibrogenic genes.