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Successfully reported this slideshow. We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime. Upcoming SlideShare. Like this presentation? In addition, Halloran et al. These patients with newly developed EPI, however, did have a tendency towards poorer quality of life. Celiac disease is a chronic inflammatory intestinal disorder that may occur in genetically predisposed people triggered by the ingestion of gluten.
In celiac disease, although exocrine pancreatic function is intrinsically normal, reduced levels of cholecystokinin release as a result of the duodenal villous atrophy, accounts for impaired gall bladder contraction and reduced exocrine pancreatic secretion [ 32 , 33 ]. The term islet-acinar axis has been used to describe the endocrine-exocrine relationship within the pancreas, whereby there is a vascular and physiologic interaction between these different cell types [ 34 ].
Pathophysiologically, diabetes mellitus can predispose to EPI and, conversely, longstanding EPI can be associated with diabetes [ 35 — 39 ]. In diabetes, there are several possible causes which can account for EPI — the lack of the trophic action of insulin and potentially of glucagon and somatostatin on acinar cells, autoimmune damage of islet cells, causing destruction of both endocrine and exocrine tissue, and decreased exocrine pancreatic secretion as a complication of diabetic neuropathy [ 36 , 37 ].
In addition, a recent article by Soave et al. Based on the study by Lebenthal and Lee [ 40 ] indicating that the duodenal fluid of newborns and infants contained no amylase and negligible lipase at least for the first month of life, all healthy term infants are exocrine pancreatic insufficient. Normally, this is compensated for by amylase and lipase present in breastmilk. However, in formula-fed infants, EPI would be expected.
In fact, a recent study by Martin et al. Thus, all infants, both term and preterm, represent the largest population of individuals with EPI. The clinical implications of developmental pancreatic insufficiency in non-breast-fed infants is unknown, but may play a role in early nutrient deficits in critically ill newborns such as the preterm infant. Expert opinion: Routinely checking for EPI in patients with chronic diarrhea, using fecal elastase, is unreliable in the absence of testing a formed stool.
A multitude of tests for EPI have been developed over the past several decades and classified as direct versus indirect measures of exocrine pancreatic function. However, many of these have poor sensitivity or specificity e.
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Unfortunately, this test is time-consuming and not easily tolerated due to bloating, abdominal discomfort, flatulence, and worsening steatorrhea. Additionally, errors can occur in stool collections and recording of fat intake [ 42 ]. The pancreas produces pancreatic elastase 1, which is a highly stable enzyme during intestinal transit [ 44 ]. This proteolytic enzyme can be measured in a fecal sample by an enzyme-linked immunosorbent assay [ 45 , 46 ].
Because pancreatic elastase is highly stable during intestinal transit, the fecal concentration correlates well with exocrine pancreatic secretion [ 45 ]. Diagnostic testing using fecal elastase has some advantages over other tests because it does not require a timed stool collection or special diet, has a high negative predictive value, and has a high sensitivity in moderate to severe EPI when formed stools are analyzed [ 8 , 42 , 47 , 48 ].
Since fecal elastase is measured as a concentration in stool, watery stools will almost invariably result in low elastase values being measured and thus this non-invasive, pancreatic function test should be performed in a clinical setting where EPI is suspected and a formed stool can be analyzed. This has replaced the more cumbersome hour fecal fat test. In addition, PERTs do not have to be stopped for fecal elastase testing since the porcine enzymes do not cross react with the human fecal elastase antibody.
Myth: PERT should be started at the lowest dose available and taken any time before a meal and at bedtime.
Enzymes: Go with Your Gut: More Practical Guidelines for Digestive Enzymes
Fat malabsorption is the predominant cause of the symptoms of pancreatic steatorrhea resulting in weight loss as well as deficiencies of fat-soluble vitamins A, D, E, and K. In patients with chronic pancreatitis, a low fat diet has been the recommendation in order to minimize the pain of this disease and, in conjunction with PERT, to effectively treat steatorrhea. However, in patients with CF, a high fat diet in conjunction with increased amounts of PERTs has been shown to improve the associated CF lung disease and thus low fat diets are no longer advocated in this disease.
Consulting a dietitian is helpful to assess nutritional adequacy [ 55 ]. In addition, smoking has been proven to be a risk factor in acute pancreatitis, chronic pancreatitis, pancreatic cancer [ 56 ], and to be associated with reduced exocrine pancreatic function [ 57 ].
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Therefore, smoking and alcohol cessation is recommended in EPI due to chronic pancreatitis. The elimination of malabsorption, reduction of maldigestion-related symptoms, and the prevention of malnutrition-related morbidity and mortality is the goal for PERT [ 55 ]. Prior to , pancreatic enzymes were not FDA regulated and had variable consistency of activity. It should be noted that the clinical trials were relatively small less than 40 subjects and tested in subjects who were known to respond to PERTs.
All pancreatic enzyme preparations are extracts from porcine pancreas pancrelipase and are available in preparations encapsulated in mini-microspheres or microtablets, which vary in particle size and pH-related release kinetics [ 58 ]. Enteric-coated pancreatic microspheres are designed to be acid resistant and pH-sensitive to protect lipase from denaturation by gastric acid.
The use of acid-suppression medications can increase gastric pH levels and theoretically improve the efficacy of PERT and decrease EPI symptoms [ 61 , 62 ]. Current data may suggest a trial of acid blockers in patients with CF who have refractory steatorrhea [ 61 — 65 ]. However, a recent retrospective study demonstrated no improvement of the coefficient of fat absorption hour fecal fat test when using a proton pump inhibitor in pediatric patients with CF [ 66 ].
Uncoated exogenous pancreatic enzymes, such as Viokase Aptalis Pharma , are thought to mix well with intragastric nutrients and rapidly release high duodenal lipase amounts for fat digestion [ 58 ]. The addition of acid-suppression medications is required to prevent degradation of non-enteric coated pancreatic enzymes [ 58 ]. Only non-enteric pancreatic enzymes have been shown to improve the pain in a subset of patients with chronic pancreatitis. The use of unprotected exogenous enzymes in combination with enteric-coated enzymes has previously been recommended for the treatment of refractory EPI [ 58 , 67 ]; however, Kalnins et al.
Dosing and frequency of administration are difficult aspects of PERT treatment since different enteric-coated microspheres are not bioequivalent in vitro [ 69 — 71 ], and there are not enough clinical studies between preparations to define in vivo bioavailability. Several countries have recommended different doses of PERT. Unfortunately, the evidence for these recommendations is relatively weak as emphasized by The Australasian Pancreatic Club in their recent study on the management of pancreatic exocrine insufficiency [ 72 ].
In addition, a study from the Netherlands by Sikkens et al. These differences in recommendations demonstrate the significant confusion over dosing and administration amongst medical practitioners. Likewise, there is no consensus over frequency of PERT administration. In , DiMagno et al.
In addition, a recent randomized three-way crossover study of 24 patients using 40, lipase units per meal compared three different administration schedules with PERT before meals, during meals, or after meals using the 13 C-MTG breath test to measure fat absorption [ 79 ].
Thus, no statistically significant differences were found between different administration schedules, however, they did recommend giving PERT during or after meals. In a patient with suspected EPI with a known history of pancreatic disease, empiric therapy with PERTs may be indicated without formal testing. A clear response would be both diagnostic for EPI as well as therapeutic. Treatment strategies for lack of response to pancreatic enzyme replacement therapy PERT. PERT should be taken with the first bite of a meal and consider adding extra enzymes during or towards the end of the meal.
The rationale for taking pancreatic enzymes throughout the meal is to mimic the action of our own endogenous pancreatic enzymes, where secretion from the gland occurs throughout a meal. These therapies have improved signs and symptoms related to EPI such as steatorrhea and abdominal discomfort, weight loss, malnutrition, and possibly even quality of life. However, there is still much confusion amongst medical practitioners over the best diagnostic approach as well as dosing and administration of PERT. Many countries have developed different guidelines regarding dosing and administration of PERT, calling out for a consensus and a practical guide for the diagnosis and treatment of EPI using exogenous pancreatic enzymes.
In addition, evidence supports that patients are being undertreated with PERT and may potentially benefit from more adequate therapy. There are two areas that need emphasis. Over the last decade, there has been a change in diagnostic approach for EPI from the unreliable qualitative stool test and the cumbersome hour fecal fat collection, to the more sensitive, but less specific, fecal elastase test, especially in patients with mild to moderate EPI.
Many physicians do not realize the need to have formed stools analyzed and thus, in chronic diarrhea, this may be problematic. Ultimately, what is critical is the early diagnosis and optimization of treatment of EPI. Second, there must be optimization of the currently available therapies for EPI. The existing studies vary on recommendations for dosing of exogenous pancreatic enzymes ranging from 25, to 80, lipase units per main meal, and there is uncertainty about administration of PERT before, during, or after the meal.
In addition, the treatment goals differ from reducing pancreatic steatorrhea and elimination of maldigestion and malabsorption, to the prevention of malnutrition-related morbidity and mortality. This is all complicated by the myriad of pancreatic enzyme formulations at a wide array of dosing strengths. Thus, it is not surprising that confusion amongst physicians exists over the optimal dosage, administration schedule, and what to aim for in PERT. MRS, Dr. SDF, and Dr.
CRM contributed equally to the review of the literature on EPI and writing and revising of the manuscript. All authors read and approved the final manuscript. He is Director of The Pancreas Center and is a worldwide leading expert on pancreatic disease and cystic fibrosis. She is an international expert on fatty acids and nutrition in preterm infants.
Maarten R. Struyvenberg, Email: ude. Camilia R.
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Martin, Email: ude. Steven D. Freedman, Phone: , Email: ude. National Center for Biotechnology Information , U. BMC Med. Published online Feb Struyvenberg , Camilia R. Martin , and Steven D. Author information Article notes Copyright and License information Disclaimer. Corresponding author.
Received Sep 8; Accepted Jan 9. This article has been cited by other articles in PMC. Abstract Background Exocrine pancreatic insufficiency EPI is characterized by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption. Discussion Many diagnostic tests are available to diagnose EPI, however, the criteria of choice remain unclear and the causes for a false-positive test are not yet understood. Summary Appropriate use of diagnostics and treatment approaches using pancreatic enzymes in EPI is essential for patients.
She also notes that one of her patients saw extreme improvements in his skin after taking enzyme supplements, and likened them to a fountain of youth 6. Enzymes have other skin health applications, too. In some instances, taking enzymes can be linked with decreased eczema symptoms, healthier looking skin tone and less severe dark circles under the eyes Emotional Wellness There may be a link between enzymes and mental and emotional wellness as well. Research has shown that there are four main nutritional causes of neurological conditions. They include a lack of proteases, inability to digest sugar, hypothyroidism and a diet high in sugar Furthermore, gastrointestinal problems are overwhelmingly common in those who suffer from neurological conditions, and digestive enzymes have a positive effect on gastrointestinal issues.
Enzymes also help the body to properly absorb vitamins and minerals, and some research suggests that certain mineral deficiencies are linked to neurological disorders. Another explanation for why enzymes support neurological health is the connection between both digestive and systemic enzymes and yeast. An overgrowth of yeast has been linked to autism, ADHD, skin problems, vaginitis, malabsorption, depression, chronic fatigue and autoimmune syndrome, among other things.
Evidence suggests that once yeast is erradicated in children with autism, their symptoms become less severe Enzymes help to reduce yeast because they have the power to break through the tough outer shell of the yeast cells so that the anti-fungal agents can destroy the yeast 7.
Think back to the nutritional causes of neurological conditions. Inadequate digestion of protein leads to inadequate acidity levels in the body, and people with this deficiency are commonly treated with medications such as Xanex. While it is important to remember that enzymes cannot treat or cure diseases, researchers suggest that they may be able to support emotional and mental health. A diet too high in sugar, which is unable to properly be broken down in such high amounts, can lead to depression, insomnia, mood swings and even panic attacks! It would be beneficial to try to find an enzyme to help with digestion and to reduce sugar intake.
Certain enzymes, such as amylase, lipase, and protease, can be used to help the thyroid to function properly 11, 4. Furthermore, enzymes help the hypothalamus to function, which has an effect on moods and awareness A diet high in digestive and systemic enzymes can support relief from anxiety, obsessive compulsion and even hyperactivity 9. This is because the neurological system is connected to the immune system and gastrointestinal system. Neurological disorders do not have one single cause that is only related to the brain.
Furthermore, enzymes aid in digestion and absorption of nutrients, supporting the effectiveness of medicines and supplements. There have been many cases where parents of children who have neurological conditions began using enzyme supplements. The parents noticed decreases in anxiety, aggression, and hyperactivity, and increases in socialization, affection, awareness and problem solving One mother noted that after she began giving her autistic child HCL-pepsin, his stools became normal and his moods greatly improved In fact, there has been a lot of research concerning the relationship between enzymes and autism.
Doctors now know that those who have autism suffer from a number of physiological disturbances that need to be treated on a biological level. This does not mean that enzymes can treat autism, but they do support the health of the nervous system, gastrointestinal system and immune system, which are three areas related to autism References 1. Enzymes, Inc. Group, Garden City, NY, Bohager, Enzymes: What the Experts Know!
One World, Prescott, AZ, Hurd and K. Whole Foods Magazine. How Sweet It Is! Living A Plant-Based Life.