9 minute read
Enteral Feeding Intolerance: Can Peptide-Based Formulas Help?
Manpreet S. Mundi, MD, FASPEN | Oley Foundation Science & Medicine Advisor
Enteral nutrition (tube feeding), which usually delivers nutrition directly to the stomach or the intestines, can help someone get the nutrition and hydration they need when they cannot drink or eat safely. Enteral nutrition can be given through nasal tubes (NG tubes), which are often used for short-term nutrition support, or percutaneous tubes (G tubes) placed right into the abdomen for long-term nutrition support. When nutrition support is needed, feeding into the gastrointestinal (GI) tract has some benefits over parenteral nutrition, which is delivered intravenously into the bloodstream. Its benefits include being more natural (through the GI tract, the way our bodies are meant to get nutrition); better immune function; better microbiome; less inflammation; and keeping the mucosal integrity of the GI tract. Also, enteral nutrition can be more costeffective than other ways of nutrition support, such as parenteral nutrition.
Despite these benefits, enteral nutrition is not without risk and can be associated with a number of complications. Nasal tubes can cause skin breakdown at the opening of the nose, or be dislodged or fall out. Percutaneous tubes can be associated with granulation tissue, infections, or leaking at the insertion site (where the tube comes out of the abdomen).
In addition to tube-related complications, patients may also have side effects related to the formula itself. This is typically referred to as enteral feeding intolerance (EFI). There is no consensus on the exact definition of EFI, however typical symptoms can include nausea/ vomiting, reflux, gas/bloating, distention, abdominal pain, diarrhea, or constipation. Although it is being used less frequently now, many clinical trials and hospital practices also considered high gastric residual volumes (GRV), or the volume of fluid in the stomach, as a sign of EFI. This practice has decreased after studies showed that checking gastric residual volumes did not improve clinical outcomes. Enteral formula intolerance can have significant negative consequences as these symptoms usually result in lower rates of feeding or the enteral nutrition being held or stopped, resulting in the patient being unable to meet their nutrition needs.
A recent review of eighty-nine clinical trials in adults showed that criteria used to define EFI varied significantly from study to study (Jenkins et al. 2022). Most common definitions of EFI involved the combination of GRV and GI symptoms, with other studies combining these with inability to meet enteral nutrition target. The cutoff for high GRV ranged from 75 ml up to 500 ml. Based on these findings, the authors recommended three key criteria to define EFI:
The patient is unable to receive at least 80% of their enteral nutrition goal.
The presence of GI symptoms such as vomiting, reflux/regurgitation, diarrhea, or abdominal distention.
The team managing enteral nutrition has eliminated other causes of the symptoms, such as infections, medications, or the patient’s anatomy (history of GI surgery such as bariatric surgery).
Despite these challenges with the definition, we do know that EFI is quite prevalent. Studies in critically ill patients have shown that EFI can occur in 30 to 40% of these patients (Gungabissoon et al. 2015; Rice et al. 2011; Wang et al. 2017). This drops to about 25% for hospitalized patients and about 20% for home enteral nutrition patients (Gungabissoon et al. 2015; Mundi et al. 2023; Wang et al. 2017). Another challenge with EFI is that there is no consensus regarding management. Typically, as part of the diagnostic criteria any other causes of GI symptoms have been eliminated. Once the symptoms are known to be related to the enteral nutrition, attempts can be made to change how the formula is being provided, such as slowing down the rate or even changing the location where the enteral feeds are provided (going from the stomach to the intestines). However, if these steps are unsuccessful, a change in enteral formula is often considered.
Enteral Formulas
Currently, enteral formulas are available in a number of categories:
Standard polymeric formulas, which typically consist of intact protein, complex carbohydrates and long-chain fatty acids, are usually recommended as the initial formula for most patients.
Blenderized tube feeding formulas, which can be either commercially blended or prepared at home, typically contain whole food ingredients and are growing in popularity.
Elemental formulas typically contain individual amino acids and smaller fatty acids and are more rarely used.
The last large category consists of peptide-based formulas, which typically use enzymes to break down the protein into smaller chains and provide more of the fats as medium chain triglycerides.
There is a great deal of data emerging regarding the use of peptide-based formulas in EFI. Theoretically, the use of enzymes to break down proteins into smaller chains and increasing the amount of di- and tri-peptides can result in better absorption, especially in those with altered anatomy. Studies have shown that transporters such as PepT1 can help with di- and tri-peptide absorption. In patients with short bowel syndrome, this transporter can be expressed in higher amounts, allowing them to absorb nutrients better with time (Ziegler et al. 2002).
Similarly, using medium chain triglycerides can improve absorption and fat utilization. Long chain triglycerides require a great deal of processing before they can be absorbed. The complicated process starts with emulsification by bile salts, which increases their surface area. They are then broken down by pancreatic lipases into monoglycerides and free fatty acids, which are absorbed into the intestinal cells. Inside these cells, they are re-esterified to form triglycerides and packaged into chylomicrons for transport through the lymphatic system, finally reaching our blood and being disseminated throughout the body. Medium chain triglycerides, on the other hand, don’t require emulsification or significant breakdown by pancreatic lipases and can be readily absorbed and released into the blood supply heading to the liver, where they can be used for energy.
Clinical studies have supported these theoretical benefits. A retrospective review of critically ill patients showed that symptoms of EFI were 15% lower with the use of 100% whey protein peptide-based formula compared to standard polymeric formula (Nguyen et al. 2024). Similarly, in hospitalized patients in various cohorts (or groups) ranging from patients who have had abdominal surgery to those with pancreatitis, peptide-based formulas led to improved weight gain, better tolerance, lower costs, and shorter length of stay (Hammaoui et al. 1990; McClave et al. 1997; Tiengou et al. 2006).
In the home enteral nutrition population, a retrospective study evaluating patients who were switched from standard polymeric formula to peptide-based formula due to EFI symptoms had a significant reduction in their symptoms of nausea/vomiting (from 42% down to 22%), diarrhea (46% down to 25%), and abdominal pain (22% down to 5%), with 49% of patients having no symptoms after the switch (Mundi et al. 2020; see figure 1). This study also demonstrated that the number of phone calls initiated by the patient, emergency room visits, and number of scheduled visits also decreased (see figure 2). Other studies have produced similar results in the adult population as well as in children (LaVallee et al. 2021; Mohamed Elfadil et al. 2022).
Summary
When someone cannot eat or drink normally without risk, enteral nutrition is better than other options, such as parenteral nutrition, because there is clear evidence of its advantage. However, enteral nutrition can also cause problems, and studies show that EFI happens frequently, both in patients who are at home and those in the hospital. Often, EFI management involves switching formulas. New research shows that using a peptide-based formula with broken down proteins and shorter fatty acid chains can improve EFI symptoms and reduce health care use. More research is ongoing to learn how this affects the patient at a cellular level and to keep improving the formulas we can offer for the best nutrition.
References
Mohamed Elfadil O, Steien DB, Narasimhan R, et al. Transition to peptidebased diet improved enteral nutrition tolerance and decreased healthcare utilization in pediatric home enteral nutrition. J Parenter Enter Nutr. 2022;46(3):626-634. doi:10.1002/jpen.2202
Gungabissoon U, Hacquoil K, Bains C, et al. Prevalence, risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness. J Parenter Enter Nutr. 2015;39(4):441-448. doi:10.1177/0148607114526450
Hamaoui E, Lefkowitz R, Olender L, et al. Enteral nutrition in the early postoperative period: a new semi-elemental formula versus total parenteral nutrition. J Parenter Enter Nutr. 1990;14(5):501-507. doi:10.1177/0148607190014005501
Jenkins B, Calder PC, Marino LV. A systematic review of the definitions and prevalence of feeding intolerance in critically ill adults. Clin Nutr ESPEN. 2022;49:92-102. doi:10.1016/j.clnesp.2022.04.014
LaVallee C., Seelam P, Balakrishnan S, et al. Real-world evidence of treatment, tolerance, healthcare utilization, and costs among postacute care adult patients receiving enteral peptide-based diets in the United States. J Parenter Enter Nutr. 2021; 45(8):1729-1736. doi:10.1002/jpen.2074
McClave SA, Greene LM, Snider HL, et al. Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis. J Parenter Enter Nutr. 1997;21(1):14-20. doi:10.1177/014860719702100114
Mundi MS, Mohamed Elfadil O, Olson DA, et al. Home enteral nutrition: A descriptive study. J Parenter Enter Nutr. 2023;47(4):550-582. doi:10.1002/jpen.2498
Mundi MS, Velapati S, Kuchkuntla AR, Hurt RT. Reduction in healthcare utilization with transition to peptide-based diets in intolerant home enteral nutrition patients. Nutr Clin Pract. 2020;35(3)487-494. doi:10.1002/ncp.10477
Nguyen DL, Schott LL, Lowen CC, et al. Characteristics and feeding intolerance in critically ill adult patients receiving peptide-based enteral nutrition: A retrospective cross-sectional study. Clin Nutr ESPEN. 2024;59:270-278. doi:10.1016/j.clnesp.2023.12.007
Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39(5):967. doi:10.1097/CCM.0b013e31820a905a
Tiengou LE, Gloro R, Pouzoulet J, et al. Semi-elemental formula or polymeric formula: is there a better choice for enteral nutrition in acute pancreatitis? Randomized Comparative Study. J Parenter Enter Nutr. 2006;30(1):1-5. doi:10.1177/014860710603000101
Wang K, McIlroy K, Plank LD, Petrov MS, Windsor JA. Prevalence, outcomes, and management of enteral tube feeding intolerance: a retrospective cohort study in a tertiary center. J Parenter Enter Nutr. 2017;41(6):959-967. doi:10.1177/0148607115627142
Ziegler TR, Fernández-Estívariz C, Gu LH, et al. Distribution of the H+/ peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome. Am J Clin Nutr. 2002;75(5):922-930. doi:10.1093/ajcn/75.5.922
