Fish Oil for Ulcerative Colitis?

A small randomized, double-blind, placebo-controlled study (E Scaioli et al. Clin Gastroenterol Hepatol 2018; 16: 1268-75) examined the use of Eicosapentaenoic acid-Free Fatty Acid Form (EPA-FFA) a component of n-3 fish oil for patients with ulcerative colitis UC).

From 2014-2016, the investigators enrolled 60 patients who had partial Mayo score <2 and fecal calprotectin >150 mcg/g who had been receiving stable therapy for at least 3 months.  Then they were randomized 1:1 to receive EPA 1000 mg BID or placebo for 6 months.

Key findings:

  • 19 of 30 (63%) EPA-FFA group compared with 4 of 30 (13.3%) of placebo-treated group had achieved the primary endpoint of a 100-point reduction in fecal calprotectin at 6 months.  OR 12.0, P<.001
  • The secondary endpoint of clinical remission was noted in 23 of 30 (77%) in the EPA-FFA group compared with 15 of 30 (50%), OR 3.29, P=.035)
  • No serious adverse effects were reported.


  • Small number of patients from a single center
  • Short follow-up
  • In those without clinical relapse, a followup colonoscopy was not performed

My take: In this study EPA-FFA was associated with lower calprotectin and higher rates of remaining in remission.  More data are needed.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Near Banff

Favorable Fish Oil Outcomes in High Risk Preterm Infants

Briefly noted: M Sorrell et al. JPGN 2017; 64: 783-88. In this small study with 13 infants (mean gestational age of 28 weeks) who had short bowel syndrome or severe dysmotility and direct bilirubin ≥4 mg/dL (mean 9.8 at enrollment), patients received a fish oil-based lipid emulsion (1 g/kg/d). They were compared with 119 GA-matched controls.

Overall, the authors found the fish oil supplement to be safe.  All patients had resolution of cholestasis. They note the difficulty of proving effectiveness and performing studies in this population.  “Neonatologists…find themselves faced with …a growing body of uncontrolled data that suggests benefits of an unapproved treatment…An attempt to perform a randomized controlled comparison of a plant-based lipid emulsion to FishLE in preventing PNALD in infants at risk was terminated early after an interim analysis revealed much lower than expected incidence of PNALD…[making] trials ethically problematic.”

My take: The data remain incomplete and make it difficult to use a therapy like Omegaven that is quite expensive (not covered) and not FDA approved.  The availability of SMOFlipid is likely to result in less usage of plant-based soy products.

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Rodin Museum

What Happened to Skepticism re: Lipid Emulsion Position Paper

A recent position paper (from ESPGHAN) (I Hojsak et al. JPGN 2016; 62: 776-92) made me wonder how different people can look at the same data and come to opposite conclusions.

In short, this article systemically reviews intravenous lipid emulsions and the risk of hepatotoxicity.  The review on the data is quite helpful.  The authors conclude that short-term use of the various emulsions currently in use do not result in a significant difference in neonates, infants and children.

The authors acknowledge that the data for long-term use of these emulsions is limited. They state that “there is evidence indicating that just tailoring and adjusting PN in children on long-term PN could improve liver disease, meaning that the focus should not only be on the type of ILE.”

“Although the quality of data are lacking there is some evidence that the use of multicomponent fish oil-containing ILE may contribute to a decrease” in liver toxicity.

What I don’t understand: The authors recommend: “it appears prudent to use multicomponent FO [fish oil]-containing ILE (GR C)” and literally the next sentence: “The present evidence base is inadequate to determine the optimal strategy for intravenous lipid supply.”

My take: I think we need to gather the data before having official position paper  recommendations.

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2min warning doesn't help

“Supplements and Safety”

There is a Frontline report (initially aired Jan 19th) on supplements.  A preview is available from the NY Times.

Supplements and Safety” –link includes a 5 minute video on fish oil. Here’s an excerpt:

The Frontline documentary investigates large outbreaks of disease tied to tainted vitamins and fat-burning supplements, including one case in which a workout supplement was linked to more than 70 cases of liver damage. The company whose products were at the center of that outbreak, USPlabs, is among 117 companies and individuals that the Justice Department filed criminal and civil enforcement actions against last year…

Despite their popularity, some studies have found that roughly three-quarters of fish oil supplements on the market do not contain the amount of omega-3 fatty acids advertised on their labels. Some have also found that fish oil supplements are prone to becoming rancid.

Fish oil supplements are widely marketed as beneficial to cardiovascular health. But the film points out that such claims are debatable at best. A majority of clinical trials have found no evidence that they protect against heart disease, according to a study published in JAMA Internal Medicine in 2014.

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Mural in Old San Juan

Mural in Old San Juan

Medical Progress for Intestinal Failure Associated Liver Disease

A recent review (WS Lee, RJ Sokol. J Pediatr 2015; 167: 519-26) provides a good explanation of the role of various intralipids and intestinal microbial dysbiosis in the setting of intestinal failure-associated lipid disease (IFALD).

The review discusses criteria for IFALD (e.g. conjugated bilirubin ≥2 mg/dL & parenteral nutrition ≥14 days), the epidemiology, and the pathogenesis. Potential risk factors and level of evidence for these risk factors is noted in Table 1.

Table 2 describes the evidence supporting suggested strategies for the prevention of IFALD. The effectiveness and recommendation levels for these strategies are generally very low and weak based on reviews by ASPEN and the American Pediatric Surgical Association.  Among the strategies, reduction of lipid emulsion to ≤ 1 g/kg/day has some of the strongest support in this table but is still regarded as level III evidence and described as “probably effective.” Other strategies reviewed included ethanol locks, multidisciplinary team management, use of ursodeoxycholic acid/bile acid supplementation, cycling of parenteral nutrition, use of prokinetics, removal of manganese and copper from parenteral nutrition, and antibiotic use to prevent bacterial overgrowth.

With regard to alternative intravenous lipids (eg. fish oil, or SMOF mixture):

  • “Although a properly powered randomized controlled trial has not been conducted, current evidence suggests that the use of FO-ILE [fish oil -intravenous lipid emulsion] is effective in reversing the established cholestasis associated with IFALD, but there is insufficient evidence for a preventative effect in neonates.”
  • “Most studies have been retrospective, used a historical comparison group, used different doses of lipid, and were conducted in patients with quite advanced IFALD.”
  • Use of FO-ILE improves biochemical parameters, but has not been shown to “improve other important long-term clinical outcomes, such as severity of hepatic fibrosis.”
  • In addition, reduced ILE and FO-ILE may result in other sequelae such as cognitive developmental delay. “Recently, lower brain weight and alterations of brain PUFA content were demonstrated in newborn piglets receiving total PN with reduced dose SO-ILE or FO-ILE compared with normal dose SO-ILE.”

My take: This review underscores how little is known about the approaches often recommended for management of IFALD.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Empty Road

Nutrition University -Part 1

While issues with nutrition are ubiquitous, among the three areas of expertise for pediatric gastroenterologists (gastroenterology, hepatology, and nutrition), it does seem that nutrition expertise receives the least interest overall.  One effort to work on this is Nutrition University (N2U) sponsored by NASPGHAN/NASPGHAN foundation.

This is the first year in which the program has been opened up to physicians who have been in practice for more than 10 years and I am looking forward to a great review. Prior to attending, the participants were asked to review previous N2U modules which are available at NASPGHAN website: 2012 N2U Course ( a good source for CME as well).

This year’s syllabus: 2015 N2U Syllabus & Presentations (posted with permission from course organizers).

Last night the meeting started off with some comments by Praveen Goday (Praveen’s training in Cincinnati overlapped with mine) who has spearheaded this effort; subsequently the faculty addressed previously submitted attendee questions.

Here’s a sampling:

Should we be recommending a low FODMAPs diet for IBS? Rob Shulman indicated that about ~70% of adults responded in one study and that a similar study in children at Baylor College of Medicine produced similar results.  However, the diet is difficult and help from a dietician/nutritionist is needed.  If there is not a response in 7-10 days, then it is likely to be ineffective.

What should be the first formula for Cow’s Milk allergy/intolerance in infancy? The recommendation for most infants (not the very sickest) was to start with a hydrolysate formula which should be effective in more than 90%.  It was suggested that amino acid based formulas be reserved for hospitalized infants and those who do not respond to hydrolysates.

What about fish oil enterally or parenterally? James Heubi(*) noted that a lot more data is needed but fish oil either enterally or parenterally may be beneficial.  Rob Shulman commented that recent work indicates that vitamin E may be an important reason why fish oil could be better than soy-based lipid emulsions.

How practical are blenderized diets for gastrostomy fed children? Catherine Karls noted that the general goal is to provide nutrients which mimic the commercial formulas but there are many important caveats for DIY (do-it-yourself formula).

  • An RD needs to supervise to assure all micronutrient needs are being met.  Using computer programs, this facilitates calculating dietary reference intakes (DRIs).
  • Many parents prefer as homebrews are perceived as more natural or holistic
  • Some children have better tolerance (eg. volume-sensitive, patients with retching)
  • Drawbacks: time commitment, additional costs (though may be cheaper for some), and concerns regarding food safety
  • Homebrews are not recommended for jejunostomy feeds (gastrostomy only) or for those with small-caliber feeding tubes (needs to be at least 14 Fr)
  • Don’t use without the assistance of an RD!

Which is better for NAFLD -low carb or low fat? Ann Scheimann stated that this question is misleading –it is a lot more complicated.  It depends on the carbs and it depends on the fat.  Fructose clearly worsens NAFLD but so does a diet high in animal fat.

What are the nutritional management recommendations for acute pancreatitis? Justine Turner indicated that too many centers continue to rely on parenteral nutrition.  Yet, guidelines recommend the use of enteral nutrition due to lower risk of poor outcomes (eg. infections when NPO and on parenteral nutrition). ‘Resting pancreas is not helpful.’ With acute pancreatitis, enzyme secretion is reduced.  Her approach is to start nasogastric (NG) feedings at about 24 hours after presentation, as long as hemodynamically stable.  She indicated that nasojejunal (NJ) feedings can be done if NG is not well-tolerated.  NJ feedings are effective at reducing enzyme secretion.  However, Praveen Goday stated that his practice was often starting with NJ feeds.  “Sometimes there is only one shot” before the ICU team starts HAL.  Both physicians indicated that polymeric formulas were probably acceptable; however, starting with semi-elemental or elemental feedings are often done, again as a practical matter to minimize the likelihood of reverting to parenteral nutrition.

What is the advice regarding children who need far less than typical calories for weight (eg. wheelchair-bound inactive child)? Generally all nutrients are being met if a child less than 10 years is receiving 4 cans of commercial formula. For children 10 and older, receiving 6 cans per day should ensure adequate nutrients.  For those who fall below this threshold, several options:

  • Reduced calorie formula (eg. Pediasure Sidekicks, Compleat Reduced) are approximately 0.6 cal/mL but have all the other nutrients
  • Supplementation: multivitamin, calcium, phosphorus, protein
  • Need to meet at least 80% of typical fluid needs, thus not much rationale for 2 cal/mL formulas. As a practical matter, if the child is urinating well, they are receiving enough fluids.

*I was fortunate to have Jim as an attending during my fellowship at Cincinnati. In fact, even before then, Jim interviewed me when I was considering Cincinnati for my pediatric residency.  He is a terrific person and amazing to work with.

Disclaimer: This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.


Two Shorts -Minimal Hepatic Encephalopathy and Fish Oil Protection

Briefly noted: JPGN 2014; 59: 689-94.  In this study, the authors took a consecutive sample of 13  children (ages 4-18 years) with non cirrhotic extrahepatic portal vein portal vein obstruction (EHPVO).  Three tests (fasting ammonia, quantified EEG, a psychometric battery) identified that minimal hepatic encephalopathy (MHE) affects approximately 50% of children with EHPVO.

Also: JPGN 2014; 59: 708-13.  In this study in 7-day old rabbits, those who receive TPN with fish oil-based lipid emulsion had protection against biochemical and liver histologic damage in comparison to rabbits who received TPN with soybean oil. Given the lack of head-to-head randomized studies in infants, this study provides some important evidence of fish oil benefit compared with standardized soybean lipid emulsion.

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