Page 47 – Practical Gastro

Nutrition Issues In Gastroenterology, Series #169

A Clinician’s Guide to Defining, Identifying and Documenting Malnutrition in Hospitalized Patients

November 2017 • Volume XLI, Issue 11

As our understanding of the effects of malnutrition on outcomes and hospital stays has evolved, it has become increasingly important for the Registered Dietitian Nutritionist (RDN) to consistently identify and communicate the degree of malnutrition present in any patient who meets criteria, in order to set up a timely treatment plan. The clinical nutrition team is positioned to spearhead the education of all appropriate providers to ensure consistent use of the approved criteria throughout the facility. This article aims to provide practical guidance for clinicians to do just that.

Malnutrition has been associated with trends toward higher acuity, higher health care cost, and poor patient outcomes. However, until recently no universal definition of malnutrition was available. As our understanding of the effects of malnutrition on outcomes and hospital stays has evolved, it has become increasingly important for the Registered Dietitian Nutritionist (RDN) to consistently identify and communicate the degree of malnutrition present in any patient who meets criteria, in order to set up a timely treatment plan. Adopting and imbedding standard language related to malnutrition in the electronic medical record (EMR) can lead to more consistent coding and tracking.

Wendy Phillips, MS, RD, CNSC, CLE, FAND, Division Director of Clinical Nutrition, Morrison Healthcare, St. George, UT Maria Browning MS, RD, CNSC, Quality Expert, Charge Management Surgical Charge Optimization Revenue Cycle Services, IU Health Methodist Hospital, Indianapolis, IN

INTRODUCTION

Most healthcare professionals will agree that malnutrition can be simply defined as inadequate calories, protein, and micronutrients required for proper tissue growth, maintenance, and repair.¹ The causes of malnutrition can be multifactorial including, but not limited to: poor nutrient intake, malabsorption, poor nutrient utilization (hyperglycemia), and/or hypercatabolism. Historically, malnutrition has had various descriptions in the literature due to the lack of a universally accepted definition. Therefore, the prevalence of malnutrition in hospitalized patients has been reported to be anywhere between 16-68%.^2-7 Regardless of the definition used, malnutrition is associated with poorer outcome,⁸ specifically: longer hospital length of stay,^4-14 more readmissions within 30 days,^14-29 more nosocomial infections,^16-29 and more pressure injuries.^24-27 Unfortunately, due to the various definitions found in the literature describing the prevalence of, and complications associated with, malnutrition, the true prevalence and consequences are still unknown.

The Academy of Nutrition and Dietetics (Academy) and the American Society for Enteral and Parenteral Nutrition (A.S.P.E.N.) joined forces to develop a consensus statement for the identification of adult malnutrition in 20121 and for pediatric malnutrition in 2014.²⁸ Clinicians and researchers are encouraged to use the criteria set forth from these documents to identify malnutrition in an effort to inform facility policies, interventions, and resource allocations. It would help the process of standardizing definitions of malnutrition if each facility reviews and approves the Academy/A.S.P.E.N. criteria for malnutrition assessment and diagnosis by all key players: clinical nutrition team, LIPs, and coders. The clinical nutrition team is positioned to spearhead the education of all appropriate providers to ensure consistent use of the approved criteria throughout the facility. This article aims to provide practical guidance for clinicians to do just that.

Malnutrition Coding: Beyond the Money

Understanding the Medicare payment structure for hospital admissions is necessary to understand the importance of adequately diagnosing malnutrition and translating the malnutrition diagnosis into International Classification of Disease (ICD), 10th revision (ICD- 10) codes.³⁰ Medicare is the largest funding source for most hospitals, and some commercial insurance companies structure their payment system similar to Medicare. Medicare does not pay hospitals directly for each expense incurred to care for patients, but rather categorizes patients into a Diagnosis Related Grouping (DRG) based on the principle diagnosis precipitating hospitalization.³¹ Payment is then based on an annual analysis of the average resources required to care for patients admitted for the same or similar principle diagnoses. Additional stratification occurs when the patient is further categorized into tiers within the DRG based on the presence of secondary diagnoses. This stratification is known as the Medicare Severity-DRG (MS-DRG) – some DRGs have one or two tiers, but the majority have three. Secondary diagnoses are those impacting clinical evaluation, therapeutic treatment or diagnostic procedures, and extend the length of stay or increase the nursing care required. They can be coded as co-morbidities or complications (CCs) or major co-morbidities or complications (MCC). See Table 1 for definition of terms. CCs and MCCs can raise the assigned tier within the DRG for the patient’s principle diagnosis. Medicare reimbursement increases to the hospital for higher tiered patient stays in order to cover the increased cost of care. Since the higher tiers have a higher relative weight (RW) assigned by Medicare, this also influences the case mix index (CMI).³¹ The CMI is an average of all of the RWs of patients with discharges within a specified time interval, and provides an index of the severity level of the patient population receiving care at that hospital. The CMI will also influence the base rate for that hospital for Medicare payment in subsequent years.

Secondary diagnoses count as CCs or MCCs and influence payments for hospital stays under Medicare’s MS-DRG Inpatient Prospective Payment System only if several conditions are met and documented in the licensed independent practitioner (LIP) progress notes.³¹ The secondary diagnosis cannot be an integral part of the principle admitting disease process itself and must affect the care provided during that hospital admission. For example, severe protein-calorie malnutrition cannot be considered a MCC for the principle diagnosis of “Failure to Thrive” because the two conditions are too similar. For principle diagnoses in which severe protein-calorie malnutrition could be listed as a MCC, there must be documentation demonstrating additional nursing care or other resources required for the patient (such as enteral or parenteral nutrition support). While clinicians recognize malnourished patients require additional resources and nursing care, this is not always clearly stated in the medical record, nor historically been adjusted for in terms of hospital reimbursement. Secondary diagnoses must be listed in the final diagnostic statement by the provider using whatever method the facility has designated (such as the problem list or the discharge History and Physical). For example, a patient may be admitted with community-acquired pneumonia as the principle diagnosis precipitating hospitalization. Secondary diagnoses may include acute respiratory failure (requiring the intervention of mechanical ventilation) and severe protein-calorie malnutrition (requiring the intervention of enteral nutrition). The acute respiratory failure and severe protein-calorie malnutrition would be listed as secondary diagnoses by the LIP in the final diagnostic statement and coded to be included in the MS-DRG assignment.

Although both acute respiratory failure and severe protein-calorie malnutrition are MCCs, only one MCC is required to increase the severity tier of the DRG. Therefore, the malnutrition cannot be considered a diagnosis that increases reimbursement in this patient, because the acute respiratory failure would have already increased the DRG and the reimbursement, even if malnutrition had not been documented and coded. However, both should be documented and coded. Beyond potentially increasing the reimbursement for providing care, the accurate identification, documentation, and coding of malnutrition is important for many other reasons. First, it encourages an increased awareness and focus on malnutrition that requires a specific intervention during that encounter and throughout the transition of care. When malnutrition is documented as a medical diagnosis and communicated through the discharge summary alerting clinicians at the next care site (such as a rehabilitation or long term care facility), prompt attention to nutrition care needs will be more likely to occur within that next setting.

Additionally, the expected length of stay (LOS), severity of illness (SOI), and risk of mortality (ROM) increase as the secondary diagnoses are coded as CCs or MCCs and the patient moves to a higher tier within the MS-DRG.³¹ This provides more realistic survival expectations for Medicare and other payers who use a method similar to the MS-DRG classifications. “Grades” that are given to a hospital and individual providers based on patient outcomes are adjusted for SOI, ROM, and CMI. The adjustment process is too complicated to explain in this article; a basic explanation is that coding for all applicable secondary diagnoses (like malnutrition) can make the hospital or provider’s grades better with the same outcomes because of the associated expected SOI and ROM. A good grade with a high CMI is an overt indication that the facility successfully cares for very ill patients. Poor grades may cause payers to remove the hospital or LIP as a provider for certain payment plans. This data is also publicly available, and patients may not seek care from institutions whose survival rates are below what is expected for a particular diagnosis. Diligence in documenting an MCC such as severe protein-calorie malnutrition not only can move the patient’s stay to a higher tier within the MS-DRG, which has the potential to direct nutrition intervention as well as help recover revenue for services, but also better represents SOI, ROM, and the resources required to care for the patient.

Finally, large-scale epidemiological studies require accurate diagnosis data available in discrete fields in the electronic medical record (EMR) that can be queried by automated data mining programs. Standardized language to describe the diagnosis of malnutrition with associated signs and symptoms ensures the interoperability and communication for that diagnosis with different EMRs, billing systems, and data mining programs used for research. An example of discrete fields would be the utilization of flow sheets with drop-down boxes that have been pre-populated with standardized language that can be clicked indicating the presence and degree of malnutrition.

Malnutrition Treatment: It Takes a Healthcare Village

The first step in identifying malnutrition in the hospitalized patient is through adequate nutrition risk screening, which is usually conducted by the registered nurse as part of the admission screening process. A validated nutrition screening tool appropriate for the patient population is recommended, such as the Malnutrition Screening Tool,³² the Malnutrition Universal Screening Tool,³³ or the Nutrition Risk Screening (NRS) 2002.³⁴ Periodically, the accuracy of the screening tool and the workflow process to notify the RDN should be reevaluated to ensure patients requiring full nutrition assessment and interventions are being identified.^35,36

Once a patient is identified as at-risk for malnutrition, or frankly malnourished, either through the nutrition screening process or other method, a referral needs to be placed to a registered dietitian nutritionist (RDN) to complete a full nutrition assessment and implement a nutrition care plan in partnership with the patient/ caregiver, physician, nurses, and other healthcare team members. RDNs rely heavily on nursing documentation to evaluate the parameters described in the malnutrition clinical characteristics consensus statements published by the Academy/A.S.P.E.N.^1,28 The RDN must communicate the presence of malnutrition and the associated signs and symptoms to the LIP responsible for the care of the patient; this will need to be included as a medical diagnosis by the LIP. This crucial step ensures the diagnosis is communicated from one care setting to the next so that nutrition intervention continues until the malnutrition is resolved.

The nutrition interventions in the care plan should specifically address the etiology, as well as signs and symptoms of the malnutrition. Often, nursing and food service staff will assist with the actual implementation of the nutrition interventions designed by the RDN, with nursing staff providing valuable documentation in the medical record about the patient’s response to care.

In some facilities, the LIP will need to place orders for at least some of the nutrition interventions per facility policy. The RDN will monitor, evaluate, and document the patient’s response to care, progress towards defined goals, making alterations to the nutrition care plan as needed, and finally document and coordinate the discharge nutrition needs to ensure appropriate nutrition follow-up after leaving the hospital.

Physicians continue to be responsible for documenting all diagnoses affecting the hospitalization or influencing the principle diagnosis causing the patient’s admission. If a patient is malnourished, this will affect the course of the hospital stay, the resources necessary to care for the patient, and the length of hospitalization required.^9-14 Therefore, malnutrition should be documented by the LIP responsible for the care of the patient whenever it has been identified by the RDN as a nutrition diagnosis.

Likewise, medical billing specialists are required to code for all diagnoses affecting the care of the patient and/or their prognosis during that hospital stay, regardless of whether or not doing so will influence reimbursement for the stay. If the RDN has provided written information about the malnutrition as a nutrition diagnosis, but the LIP has not added it also as a medical diagnosis, then the billing specialist should query the LIP to check for agreement with the RDN. He/she may also query the RDN for documentation clarification if necessary.

Documentation Guidance for RDNs and LIPs

Since the malnutrition diagnosis must be documented by the LIP for it to become part of the official record of care from one healthcare facility to the next, RDNs need effective communication strategies to notify the LIP when a patient is identified as malnourished. Ideas to accomplish this are included in Table 2. A suggested sample charting template for RDNs is included in Table 3 with ideas on how this can coordinate with the LIP’s documentation. Documentation must be sufficiently detailed and measurable, and specific to the patient to support Medicare billing compliance audits that may be conducted by Medicare’s Recovery Audit Contractors or the Office of the Inspector General. See Table 4 with examples for specific and measurable documentation.

Building the Foundation: Success Story of Documentation

Streamlining and standardizing the documentation process as described above can lead to drastic improvements in identifying all degrees of malnutrition within the hospital setting. In 2013, Indiana University (IU) Health identified a significant opportunity to improve the diagnosis of malnutrition at their Adult Academic Health Center (AHC). The AHC consists of 2 major hospitals including: level one trauma services, comprehensive transplant services, the largest neurosurgery center in the state, and destination care for all ranges of oncology services, as well as many others. Despite providing high-level care for acute and chronically ill patients, in 2013, malnutrition was coded as a secondary diagnosis in only 5.5% of patients discharged from the 2 facilities combined.³⁷ As a process improvement intervention, standardized language using the malnutrition clinical characteristics criteria from the consensus statement1 was developed and imbedded within the EMR in 2014 allowing the clinical nutrition team to unify their approach to the diagnosis of malnutrition Additionally, with the support of IU Health Information Services and the Statewide Advanced Provider Team, approval was gained to allow for RDN documentation to automatically populate LIP documentation. Within the first year of implementation, total patients discharged with a diagnosis of malnutrition increased from 2900 to 4969 encounters, a 71% increase. More specifically, severe protein-calorie malnutrition diagnoses increased from 459 to 2081 encounters, a 353% increase. Ultimately, the end result was an increase in total discharges with a malnutrition diagnosis from 5.5% to 10%.³⁷

The increased number of discharges with a malnutrition diagnosis led to improved communication of the nutritional state of the patient and required interventions implemented to remedy the malnutrition in the transition of care from the acute care hospital to home, long term care facility, or inpatient rehabilitation facility.

Consistent with previous studies,^7,12 the costs associated with treating malnourished patients were higher in IU Health’s population. Despite making up only 6% of the population, patients diagnosed with malnutrition made up nearly 12% of the total variable direct cost for patients admitted during a 30-day period (Table 5). Therefore, increasing awareness of the prevalence of malnutrition and the associated necessary interventions to treat it is an important step towards reducing overall healthcare costs.

CONCLUSION/CALL TO ACTION

Focusing on nutrition assessment, diagnosis, documentation, and intervention led to a significant improvement in identifying patients at nutrition risk requiring intervention at IU Health. Continued attention must be given by the entire healthcare team to ensure ongoing success. It is essential for RDNs to be diligent in their role to identify malnutrition, communicate with the LIP and other healthcare team members, and most importantly, implement meaningful interventions. Patients identified with malnutrition during their hospital stay should have clear instructions for continued nutrition repletion communicated to all appropriate healthcare team members and documented in the discharge summary. Standardizing how malnutrition is defined and documented with details specific to the individual patient will help facilities move towards meaningful and effective assessment, diagnosis, and intervention. In order to conduct studies within and beyond our own institutional walls, RDNs should agree to use the standards as defined by the Academy/A.S.P.E.N. Consensus Statements of 2012 (adults)1 and 2014 (pediatrics)28 and build this into daily practice. First and foremost the goal is to improve care and patient outcomes, benefiting not only the patient and families, but also the providers and institutions. Consistent documentation and coding leads to a better understanding of disease through the ability to mine large amounts of data to determine which diagnoses are most often comorbidities of each other and the related implications. Correlating malnutrition with quality metrics such as length of stay, blood stream infections, wound healing, anthropometrics, readmission and mortality will allow for improved understanding of implications and lead to more targeted therapy. An understanding of population health determinants requires appropriate documentation and coding of protein-calorie malnutrition to inform populated based interventions. Acknowledements A special thank you to Kate Willcutts, DCN, RD, CNSC, University of Virginia Medical Center, Charlottesville, VA and Terese Scollard, MBA RDN LD FAND, Providence Health and Services, Portland, Oregon, for their expertise and editorial suggestions.

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Nutrition Issues In Gastroenterology, Series #168

Nutritional Approaches to Chronic Nausea and Vomiting

October 2017 • Volume XLI, Issue 10

Nitin K. Ahuja

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In addition to a relative lack of definitive diagnostics and effective therapies, maintenance of adequate nutritional intake can represent a significant challenge for patients with chronic nausea and vomiting. This brief review will consider the existing evidence basis for nutritional approaches to a variety of non-structural causes of chronic nausea and/or vomiting, including gastroparesis, chronic nausea and vomiting syndrome, functional dyspepsia, cyclic vomiting syndrome, and rumination syndrome.

Nitin K. Ahuja, MD, MS, Assistant Professor of Clinical Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

INTRODUCTION

For a variety of reasons, chronic nausea and vomiting can be difficult complaints to manage clinically. In cases of severe or refractory symptoms, quality of life can be markedly diminished, which often corresponds with significant healthcare resource utilization.¹ Objective testing modalities beyond endoscopy and scintigraphy are also limited, leading to a sometimes frustrating lack of etiologic specificity and often empiric patterns of therapeutic decision-making.

Regardless of governing diagnosis, the role of nutrition in the setting of chronic nausea and vomiting can be vital. Given a tendency within this patient population toward postprandial symptom exacerbation, there is keen interest in potentially mitigating dietary strategies. Chronic nausea and vomiting also may limit the adequacy of nutritional intake, which can necessitate consideration of enteral or parenteral feeding alternatives. While several options exist for pharmacologic and mechanical intervention among patients with chronic nausea and vomiting, this review will focus on nutrition-based approaches to their longitudinal support.

Etiology and Nomenclature

Recognizing the diverse and often overlapping diagnostic categories for chronic nausea and vomiting is a useful preface to considering nutritional management in the face of these symptoms (Table 1). Gastroparesis, defined as a clinical syndrome of gastric retention with objective evidence of delayed gastric emptying, is a commonly suspected etiology. When gastric emptying time is normal, however, and mucosal abnormalities, mechanical gastric outlet obstruction, and metabolic disturbances have been excluded, a diagnosis often relies on clinical patterns. With its latest iteration of diagnostic criteria (Rome IV), the Rome Foundation offered a revised classification for this latter set of patients, combining “chronic idiopathic nausea” and “functional vomiting” into the single category of “chronic nausea and vomiting syndrome (CNVS).” CNVS is formally defined as bothersome nausea or episodic vomiting, either of which must occur at least once weekly, at the exclusion of regurgitation, rumination, disordered eating behaviors, and underlying structural or systemic processes.²

Some investigators have questioned the importance of distinguishing gastroparesis from chronic nausea and vomiting with a normal gastric emptying time (sometimes called “chronic unexplained nausea and vomiting” or “vomiting of unexplained etiology”) given that the clinical presentation and management of these two entities are often strikingly similar.³ Functional dyspepsia (FD), a related Rome IV diagnosis that emphasizes post-prandial pain or fullness as the primary complaint, also includes the possibility of co-morbid chronic nausea (though usually without significant vomiting). Alternative nomenclature, including “gastroparesis-like syndrome” and “gastric neuromuscular dysfunction,” has been proposed to reflect the possibility that, along a spectrum of transit time measurements, patients with chronic nausea (with or without associated bloating, abdominal pain, subjective fullness, and early satiety) may reflect common pathophysiologic mechanisms.4³

Other potential explanations for chronic nausea and vomiting, such as cyclic vomiting syndrome (CVS), abdominal migraine, and rumination syndrome, have distinct historical features, but are likewise limited by a lack of clear objective metrics. CVS is defined according to Rome IV clinical criteria as episodes of vomiting stereotyped by acute onset and short duration with absence of vomiting between episodes. On the basis of phenomenological similarities and associations with migraine headaches, abdominal migraine is hypothesized as a close relative of CVS, the former typified more prominently by pain than by nausea. Rumination syndrome is a behaviorally mediated disorder defined by Rome IV criteria as the persistent regurgitation of recently ingested food, often within 30 minutes of meal completion; regurgitation, in turn, is qualitatively distinguished from vomiting by its effortless quality and usual dissociation from prodromal retching.² Chronic nausea and vomiting complaints might also reflect disordered eating, excessive cannibis use, or dysmotility processes distal to the stomach (e.g. intestinal pseudo-obstruction).

Gastroparesis and Chronic Nausea and Vomiting Syndrome

Gastroparesis is usually thought to arise from autonomic nerve injury related to diabetes, surgery, or antecedent infections, though the largest disease subcategory remains idiopathic.⁵ Aside from the need for blood glucose optimization in patients with diabetes, nutritional recommendations in gastroparesis tend not to be etiologically specific. Indeed, some practitioners regard these recommendations as broadly relevant enough to apply, at least in part, to patients with symptoms of gastroparesis and a normal gastric emptying time, though specific data are lacking regarding optimal nutritional strategies within this population.⁶

Dietary Symptom Management

American College of Gastroenterology (ACG) guidelines advocate dietary interventions as the first- line strategy for gastroparesis management (Table 2). Traditional dietary recommendations to minimize symptoms and maximize tolerance of oral intake include: small, frequent meals (=4/day) given the tendency toward gastric retention; an emphasis on liquid nutritional sources given relative preservation of liquid emptying function in gastroparesis; restriction of excess fat intake with solid meals given its deleterious effects on stomach emptying; and restriction of fiber intake given the risk of bezoar formation.⁷ The narrowness of these restrictions is often organized in a stepwise manner in accordance with symptom severity, such that patients are ideally graduated from thin liquids to tolerable solids as their symptoms improve.⁸

Despite the longstanding nature of these recommendations, they are largely rooted in physiologic models and expert opinion rather than direct, trial- based observation.⁹ A recent study of 12 patients with gastroparesis demonstrated increased post-prandial symptom severity with high-fat versus low-fat meals and with solid meals versus liquid meals.¹⁰ A slightly larger study by the same group inventoried specific foods in a cohort of 45 patients with gastroparesis, identifying a trend toward fatty, spicy, acidic and roughage-based foods as reliable symptom triggers, while bland, sweet, salty, and starchy foods were comparatively well tolerated.¹¹

Relatively newer strategies for oral nutrition in patients with gastroparesis include the small particle size diet, which emphasizes food that is easily mechanically processed to the consistency of a mashed potato. Within this framework, easily digestible foods include, for example, avocados, processed cheese, and other foods that can be pureed, mixed, or cooked to the consistency of mashed potatoes. Poorly digestible foods, by contrast, include seeds, grains, and fibrous, unpeeled fruits and vegetables. A randomized controlled trial of the small particle size diet among patients with diabetic gastroparesis demonstrated significant reductions in the severity of nausea/vomiting symptoms (as well as postprandial fullness and bloating) relative to a traditional diabetic diet. These symptom reductions were noted despite a significantly higher amount of fat in the intervention diet, suggesting that, with further study or in particular patient subsets, some nutritional recommendations may take priority over others.¹²

Other investigators have considered the utility of reducing fermentable carbohydrate loads (e.g. fermentable oligo-, di-, monosaccharides and polyols; FODMAPs) among patients with gastroparesis, particularly in light of the benefits such diets yield in the context of irritable bowel syndrome.¹³ Retrospective, questionnaire-based analysis has suggested an association between high FODMAP intake in gastroparesis and increased abdominal pain and reduced quality of life, though no significant trend was noted with respect to nausea and vomiting.¹⁴

Table 3 offers more targeted recommendations based on the broad strategies outlined above (but should be supplemented with other published materials and consultation with a dietitian for the purposes of patient counseling). Dietary strategies may also include the consumption of herbal compounds with previously demonstrated antiemetic properties. While ginger preparations have not been rigorously studied in the context of gastroparesis or CNVS, they have demonstrated benefit in chemotherapy-induced nausea and hyperemesis gravidarum, with a putative mechanism related to accelerated gastric emptying and increased antral contractions.^15-16 Researchers have tended to study ginger as a powdered extract in dose ranges of 250-1,000 mg, though anecdotal benefits have also been reported from a variety of commonly available ginger products, including raw and crystallized ginger as well as ginger ale.11 A separate compound of nine herbal extracts called STW5 (marketed from Germany as Iberogast) has demonstrated the ability to promote antral contractions and increase proximal gastric volume, suggesting a possibly beneficial role in gastroparesis, though it has not been formally studied in this population.¹⁷

Nutritional Support

The propensity toward malnutrition among patients with gastroparesis is well established with regard to overall caloric intake as well as vitamins and minerals. Data suggest that particularly common micronutrient deficiencies include iron, folate, thiamine, calcium, magnesium, phosphorus, zinc, and Vitamins B12, C, D, E, and K.^18-19 Importantly, overweight status precludes neither the diagnosis of gastroparesis nor the possibility of malnutrition, as recent research indicates that weight gain may be due to significantly reduced energy expenditure in this population relative to healthy controls.²⁰

Among patients in whom oral feeding is deemed inadequate, enteral supplementation is preferred to parenteral supplementation due to the former’s relative safety, lower costs, and ease of use. Common thresholds for considering the initiation of enteral therapy include: unintentional, progressive weight loss (e.g. greater than 5-10% over 3-6 months, or consistently below agreed upon goals); frequent hospitalizations for dehydration or metabolic disarray; an inability to reliably take oral medications; and an otherwise unsustainably low quality of life or failure to thrive. The vast majority of patients will tolerate standard enteral formulations, though hospitalization is usually required for initiation of feedings, particularly among patients with labile blood glucose control or acutely severe symptoms.²¹

ACG guidelines for gastroparesis management recommend a trial of nasojejunal feedings prior to placement of a percutaneous feeding tube terminating in the jejunum in order to bypass the stomach. Keeping a jejunal tube in an appropriate position can be a challenge, however, particularly in patients with persistent vomiting. Anecdotal strategies to avoid displacement include minimizing the pre-pyloric distance traversed by the tube and locating its tip as distally as possible, though even with optimal initial positioning, endoscopic or fluoroscopic replacement may become necessary. Direct jejunostomy placement can also mitigate the likelihood of tube displacement but is relatively more technically challenging and precludes the possibility of gastric venting.7 Little data is available regarding preferred enteral supplementation strategies in symptomatic patients with a normal gastric emptying time. In practice it may be more difficult to make the case for jejunal tube placement in patients without a formal diagnosis of gastroparesis, though cohort studies acknowledge the potential need for enteral feeding in this population as well.²²

Other Causes of Chronic Nausea and Vomiting
Functional Dyspepsia

Similar food-based symptom triggers (fried, fatty, spicy foods, along with carbonated beverages) have been identified in the gastroparesis and FD populations.²³ While the mechanistic relationship between these two conditions is not yet definitively established, intriguing arguments have been made regarding the likely interplay among dietary fat, gastrointestinal signaling hormones, and aberrant gastroduodenal bolus transit giving rise to distressing visceral sensations in FD.^24-25 These hypotheses may have relevance for other chronic nausea syndromes as well. Recently published ACG guidelines do not recommend routine use of complementary and alternative modalities such as herbal preparations for FD, citing insufficient evidence.²⁶

Cyclic Vomiting Syndrome (CVS) and Abdominal Migraine

While CVS manifestations can be marked by significant heterogeneity, diet plays a significant role in a subset of patients with this disorder. Potential triggers of stereotyped vomiting episodes can include prolonged fasting and catabolism associated with interceding illness, in which case prophylactic nutritional recommendations include supplemental carbohydrates between meals, before exercise, and at bedtime. Specific food-related triggers sometimes attributed to CVS include chocolate, cheese, caffeine, and monosodium glutamate (MSG), which, once identified in a given patient, should be avoided.²⁷ Such recommendations are sometimes broadened to exclude all foods generally implicated in migraine provocation (including citrus, pork, shellfish, game, gravies, yeast extract, and alcohol), attesting to the putative clinical proximity of CVS and abdominal migraine.²⁸ Interest in the dietary management of these conditions spans several decades; a low-oxalate diet (e.g. avoidance of carrots, onions, rhubarb, spinach, chocolate, and tea) was once advised in the 1970s for CVS and abdominal migraine, which at the time were deemed synonymous.²⁹

Rumination Syndrome

While the therapeutic mainstay for rumination syndrome is behavioral, many experts advocate a multidisciplinary team of providers, particularly in severe cases. As with chronic nausea and vomiting of any etiology, the perspective of a dietitian can be quite valuable for accurately assessing caloric deficits and goals. The use of temporary enteral feeding modalities (e.g. nasogastric or nasoduodenal tubes) can also help meet patients’ nutritional needs while targeted behavioral interventions are being pursued.³⁰

CONCLUSION

Formalized dietary recommendations for patients with chronic nausea and vomiting hinge on diagnostic categories whose boundaries have been subject to ongoing revision. The clinical relevance of gastric emptying delay, in particular, has been called into question, suggesting that oral feeding recommendations for gastroparesis may be at least partially applicable to symptomatic patients with normal scintigraphic results. Enteral supplementation is preferred when oral nutrition is deemed inadequate, with post-pyloric feedings perhaps easier to rationalize in the setting of documented gastroparesis. Particular foods have been identified as typical symptom triggers in gastroparesis, FD, CVS, and abdominal migraine, and avoidance of these foods can be considered on an empiric basis. Areas ripe for further study include the precedence of dietary content versus consistency in the management of gastroparesis; optimal thresholds and locations for enteral feeding in various patient subsets; and any relevant distinctions between gastroparesis, FD, and CNVS that might impact individual strategies of dietary optimization.

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Frontiers In Endoscopy, Series #37

Melanoma Metastatic to the Ampulla of Vater Diagnosed via EUS-Guided Core Biopsy

July 2017 • Volume XLI, Issue 7

Zoey Bridges,

Isaac Lloyd,

Douglas G. Adler

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In this article, we discuss a rare presentation of metastatic melanoma to the ampulla where an endoscopy and endoscopic ultrasound were vital in evaluating the patient and obtaining core biopsies of the lesion. Proper tissue acquisition was made possible with EUS-FNB for pathology interpretation, showing the value of this technique.

Zoey Bridges,¹ Isaac Lloyd MD,² Douglas G. Adler MD, FACG, AGAF, FASGE¹ ¹University of Utah School of Medicine, Department of Internal Medicine, Division of Gastroenterology and Hepatology, ²University of Utah School of Medicine, Department of Anatomic Pathology, Huntsman Cancer Center, Salt Lake City, UT

CASE HISTORY

A 69 year old female had a history of a metastatic melanoma to the left groin without identification of a primary site 4 years prior to presentation. The groin lesion was resected and one out of 14 nodes was positive for melanoma, and the patient was ultimately staged as having pTx N1b M0 stage IIIC melanoma. At that time, she was treated with ipilumimab.Three years prior to presentation she developed a left inguinal lymph node recurrence, which was resected. This year, the patient underwent a surveillance CT scan which revealed a generous ampulla and elevated serum liver chemistries and was referred to endoscopy. At endoscopy, the ampulla was generous without obvious mucosal neoplasia. (Figure 1) Endoscopic ultrasound revealed a hypoechoic, 15x19mm mass lesion in the ampulla below the mucosa. (Figure 2) The lesion compressed the CBD, but the duct was still patent. The lesion was sampled via EUS-guided core biopsy using a 22 gauge core needle. Pathologic analysis revealed metastatic melanoma. (Figure 3). The patient was referred back to oncology and initiated treatment with pembrolizumab.

Discussion

Malignant melanoma develops from melanocytes mainly present in the skin, eyes, meninges and gastrointestinal (GI) mucosa, which can arise anywhere from the mouth to the anus. Melanoma is rare, comprising only 1-3% of all tumors.¹ While the primary site of melanoma is the skin, it is known that melanoma can metastasize to the GI tract.^2,3 The propensity of a primary malignant tumor to metastasize depends on the Clark staging, with >70% of Clark level III and Clark level IV lesions involving the GI tract.⁶ Metastatic melanoma has been seen in the esophagus, stomach, small intestines, and colon. 1-4% percent of patients with malignant melanoma show clinically apparent gastrointestinal tract involvement during the course of their disease and are diagnosed ante mortem, while up to 60% of all patients with melanoma are found to have metastases at autopsy.⁴ Due to these findings, some have recommended that all patients with known melanoma should be screened to rule out any gastrointestinal spread.⁴

The clinical presentation for patients with metastatic melanoma can be asymptomatic or can include the following: abdominal pain, upper or lower GI tract bleeding, anemia, weight loss, intestinal obstruction, perforation, or intussusception.^1,5 The anorectal region is the most common site for primary gastrointestinal melanomas, due to the presence of melanocytes.⁷ On the other hand, metastases of the GI tract are seen more frequently in the small intestines (35% to 97%).^6,7 Reports on the prevalence of metastatic melanoma in the gastrointestinal tract show 0.1-0.5% cases in the esophagus, 5%-50% cases in the stomach and duodenum, and 5%-32% cases in the colon.⁷ When examining these rates separately, reports found 12%-19% occurrence of malignant melanoma in the duodenum and 24%-26% in the stomach.8 The average time from initial diagnoses to the finding of intestinal metastases ranges from 21.6 months to 54 months.⁷

While primary GI and biliary melanomas are rare, it can be difficult to distinguish between a primary mucosal, metastatic GI, and biliary melanoma from an unknown or regressed primary site.⁹ If a primary lesion has already been diagnosed, the clinician can usually determine that the melanoma in the GI tract is in fact metastatic.9 This particular patient did have a prior history of melanoma that had metastasized to other areas. Metastases of the GI tract often occur late in the history of the disease and have an overall poor prognosis.¹⁰ Once melanoma has metastasized to the GI tract and other visceral sites, the median survival is four to nine months for these patients.¹¹

While it is uncommon to find metastatic melanoma in the biliary tree it has been previously documented.¹⁰ Unfortunately, the incidence of isolated metastases to the ampulla is far less known with only a few reports to analyze.^10,11,12 The literature separates the cases of primary biliary tract melanomas and ampullary melanomas. One publication suggests that many of the ampullary melanomas may have metastasized from cutaneous or vaginal primary melanoma.⁹ Metastatic melanoma to the common bile duct can present itself as a lesion located above the ampulla. One study reported the metastatic melanoma of the common bile duct extending to the ampulla and involving the gall bladder.⁹ This particular case found the patient’s lesion in the ampulla compressing her CBD. At postmortem examinations, 6% of patients with a known malignant melanoma have unexpected bile duct involvement while 15% with metastatic melanoma have gallbladder involvement.¹¹ Melanoma metastatic to the ampulla is rare and can cause biliary obstruction.^10,11 Patients diagnosed with metastatic melanoma of the ampulla presented symptoms of nausea, vomiting, cholestasis, and melena.¹⁰

The appearance of metastases during an endoscopy may take the form of ulcers, nodules, or polyps, which may be pigmented or amelanotic.⁶ Diagnostic yield of biopsy from the margins of these ulcerations or lesions is >90%.⁶ The 15x19mm mass lesion found in the patient’s ampulla below the mucosa was analyzed and a EUS-guided fine needle biopsy was taken. The 22 gauge needle used to collect the biopsy is specifically used in diagnosing pancreatic and non-pancreatic lesions where the tip of a fine needle aspiration (FNA) is not optimal.

Recent months have seen the development of biopsy needles designed for core tissue acquisition that provide sufficient tissue for histologic evaluation.¹³ One multicenter study on EUS-FNB reported on the histological specimens being adequate in 89.47% of the patients and having a diagnostic yield of 92.9% of patients.¹⁶ Core EUS-FNB needles can provide higher histologic yield despite requiring fewer needle passes compared to the standard EUS-FNA needles.¹⁴ The endoscopist, for this particular case, saw it beneficial to use a EUS-FNB, with a 22-gauge needle, to sample the lesion on the patient’s ampulla.

EUS-FNB needles can come in a variety of gauge sizes, including 19, 22, and 25 gauge. While the larger diameter needles may provide more tissue, there can be instances where 19 gauge needles are associated with an increase in blood and cellular debris contamination, adverse events, or technical failures.^15,16 A prospective study comparing of a 25-guage and 22-gauge FNB needles found the diagnostic accuracy of the two were 98% and 95%, respectively. While the 25-gauge needle produced adequate core biopsies for histological examination in 87.5% lesions in comparison to 82.1% of lesions that were sampled with a 22-gauge needle.¹⁵ A study on EUS guided fine needle biopsy (FNB) sampling compared a forked-tipped biopsy needle to a FNA needle found that the FNB needle provided a higher yield of core tissue with fewer passes.¹³ This particular study found histology cores in 95% of the fine needle biopsy samples in comparison to only 59% of the fine needle aspirate samples. The median number of passes for FNB needles during this study was two while four passes remained the median for FNA needles.¹³ Another result of this particular study was that the authors found a diagnosis of a specific lesion type was obtained with no more than two passes in 80% of the FNB group but only in 14% of the FNA group.

Another study analyzed two specific core needles; one with a reverse-bevel design and another with a 6-cutting edge and opposing bevel design. In this study, 99% of the specimens obtained with the opposing bevel needle were adequate for histopathologic interpretation in comparison to only 87% of the samples obtained from the needle with the reverse bevel.¹⁴ This study also found the opposing bevel tipped needle providing higher sensitivity (90.1% vs 71.1%) and overall accuracy (92% vs 74%) than the reverse bevel needles. The FNB needle used during our patient’s EUS provided adequate core biopsies for pathologists to complete a histopathologic interpretation. The sufficient amount of core collected aided the pathologists in diagnosing the lesion as metastatic melanoma in the ampulla.

While endoscopy can help identify any ulceration or lesion, metastatic melanoma may be completely amelanotic with a variable cytological appearance. In order to confirm the diagnosis of malignant melanoma immunhistochemical stains are needed; the S100 sensitivity varies between 33-100%, HMB-45 antibodies has sensitivity between 80-97%, but the specificity is high (100%).^1,10 Proper tissue acquisition is important in diagnosing these lesions because an adequate sample must be obtained for the immunohistochemical stains. The EUS-guided core biopsies collected in this case were more than for diagnosing the patient’s lesion as metastatic melanoma and provided tissue for both cytologic and histologic analysis.

Overall, metastatic melanoma in the GI tract is often times asymptomatic or not discovered until autopsy. This patient had a rare presentation of metastatic melanoma to the ampulla. An endoscopy and endoscopic ultrasound were all vital in evaluating the patient and obtaining core biopsies of the lesion in her ampulla. Proper tissue acquisition was made possible with EUS-FNB for pathology interpretation, showing the value of this technique.

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Nutrition Issues In Gastroenterology, Series #182

Revisiting Vitamin B12 Deficiency: A Clinician’s Guide For the 21st Century

December 2018 • Volume XLII, Issue 12

Andrew P. Copland,

Brian J. Wentworth

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Vitamin B12 (cobalamin) deficiency is a common disorder encountered across various medical and surgical disciplines. Traditional diagnosis has relied on serum cobalamin quantification; however, accumulating evidence suggests that a significant proportion of cases are missed without additional workup. This review discusses the various etiologies of B12 deficiency, provides a practical approach to diagnosis, and summarizes the available nutritional and medical literature regarding management.

Brian J. Wentworth MD, Fellow Physician, PGY-4, University of Virginia Health System, Division of Gastroenterology & Hepatology Andrew P. Copland MD, Assistant Professor of Medicine, University of Virginia Health System, Division of Gastroenterology & Hepatology, Charlottesville, VA

INTRODUCTION

Vitamin B12 (cobalamin) is a water-soluble vitamin that serves as cofactor for three major cellular reactions converting:

1. Methylmalonic acid (MMA) to succinyl coenzyme A,
2. Homocysteine to methionine, and
3. 5-methyltetrahydrofolate to tetrahydrofolate.

The first reaction is a key step in the tricarboxylic acid (TCA) or Krebs cycle within the mitochondria to generate energy (adenosine triphosphate), while the latter two reactions ensure unimpeded DNA synthesis. In addition, vitamin B12 (B12) is essential for myelin synthesis and maintenance within the nervous system and also plays a role in bone marrow erythropoiesis.^1,2

B12 deficiency is quite common. Estimates range from 40% to 80% in developing nations;³ surprisingly, approximately 6% of people aged less than 60 years and nearly 20% of adults older than 60 years are B12 deficient in the United Kingdom and the United States.⁴ Despite its high prevalence, however, B12 deficiency often remains undiagnosed and may present subtly in patients. An understanding of the basic physiology of B12 absorption will help the clinician contextualize how deficiency may develop. Appreciating the limitations of current diagnostic strategies is key to effective clinical practice.

Physiology

Vitamin B12 is one of the essential vitamins as it cannot be synthesized by human metabolism. Bacteria and archaebacteria synthesize B12 through aerobic and anerobic pathways, respectively.⁵ Human colonic flora are also able to produce B12, yet its location distal to the terminal ileum prevents absorption.⁶ To achieve an adequate daily intake of 2.4µg for adults (2.6µg for pregnant women and 2.8µg for lactating women), humans must obtain B12 from animal products including meat, seafood, dairy, and fortified cereals.⁷ Interestingly, ≤1% of free cobalamin is absorbed at the epithelial border in the terminal ileum. The remainder is stored in the liver and muscles, with a half-life of 1-4 years.⁶

In food, B12 is protein-bound. As food reaches the stomach, gastric parietal cells secrete pepsinogen and intrinsic factor (IF). Pepsin, the activated form of pepsinogen, cleaves food-bound B12 allowing it to bind to haptocorrin (R-binder). In the small bowel, pancreatic proteases break this B12-haptocorrin complex, forming a new B12-IF complex. The B12-IF complex travels to the terminal ileum where it is absorbed via the receptor complex cubam.^6,8 After absorption, B12 binds to either haptocorrin for transport to the liver, or transcobalamin to form holotranscobalamin, which facilitates incorporation into cells.8 In contrast, synthetic or unbound B12 does not require pepsin to bind to IF and 1-2% can be passively absorbed throughout the GI tract without intrinsic factor or the presence of an ileum.⁹

Both enteral nutrition (EN) and parental nutrition (PN) are able to provide adequate daily requirements for B12, assuming the patient is on daily PN¹⁰ or receives the volume of EN needed to provide the daily requirement. A recent review of 62 enteral formulas determined on average each product provided > 200% of the recommended daily amount (doses of 1500 and 2000 Kcal/day).¹¹ Although jejunal feeding bypasses the stomach, the passively absorbed synthetic B12 in commercial products is adequate to prevent deficiency.⁸

Pathophysiology

In addition to inadequate B12 intake, there are numerous steps in the B12 absorptive pathway where disease may strike (Table 1). Gastric parietal cell loss secondary to autoantibodies (autoimmune gastritis) or surgical removal causes loss of hydrochloric acid and intrinsic factor production.¹² Autoimmune gastritis (AIG) has a prevalence of 2.5-12% without sex preference; all ages may be affected,¹³ but a large series reported a median age range of 70-80 years. It is associated with the presence of autoantibodies to parietal cells and/or intrinsic factor. Risk factors for development of AIG include a history of autoimmune disease (particularly thyroid disorders), northern European heritage, HLA DRB1*03 and DRB1*04 genotypes, and age over 30.¹⁴ Over time, pernicious anemia may develop, which is defined as the presence of anemia, low serum B12, gastric body atrophy (with resultant atrophy of oxyntic glands and hypochlorhydria), and the presence of autoantibodies. The duration from onset of AIG to development of pernicious anemia is not well described in the literature, but some reports suggest a latency of as long as 20 years.²

Intestinal malabsorption of food-bound B12 has several physiologic mechanisms, including ileal resection or active inflammation, pancreatic insufficiency, congenital defects (Table 1), and an altered intestinal microbiome.⁴ Small-intestinal bacterial overgrowth (SIBO) has increased in prevalence over time and may interfere with protein-bound B12 absorption due to competitive inhibition by abnormal ileal flora.¹⁵

Some medications can also interfere with B12 absorption. Chronic use (2+ years) of acid-suppressing medications, including h3 receptor antagonists (h3RAs) and proton-pump inhibitors (PPIs), are associated with a higher likelihood of deficiency. The proposed mechanism involves a loss of gastric acid required to activate pepsinogen to pepsin in the stomach, disabling the cleavage of B12 from its associated R-protein.¹⁶ Long-term metformin use has also been associated with B12 deficiency; however, a true estimate of effect size remains elusive.¹⁷ Unlike acid suppressants, the mechanism for B12 deficiency is less well understood for metformin, and may relate to interference of calcium-dependent membrane action necessary for B12-IF complex absorption in the terminal ileum.¹⁸ Recreational nitrous oxide (N2O) use in adolescent and young adult population may also precipitate B12 deficiency with high dose or chronic abuse. N2O irreversibly oxidizes the cobalt ion of B12, interfering with its ability to be a cofactor to methionine synthase, leading to downstream impairment of myelin production.¹⁹

Clinical Manifestations

The sequelae of B12 deficiency in adults ranges widely in severity. Given the hepatic storage of inactive B12, onset to overt deficiency may take up to 10 years.² Mild deficiency may present only as fatigue. As B12 deficiency becomes more severe, skin hyperpigmentation, glossitis, cardiomyopathy and infertility can be seen.^2,4 Thrombosis, including atypical presentations such as cerebral venous sinus thrombosis, may occur as a result of hyper-homocysteinemia induced by severe B12 deficiency.²⁰ Bone marrow involvement is common and pancytopenia may develop in severe deficiency. Megaloblastic anemia is most frequently seen, although patients with AIG may initially demonstrate iron deficiency (gastric acid is necessary for duodenal iron absorption), before B12 deficiency is diagnosed.²⁰ Neurologic dysfunction is not uniform and can present with demyelination of the posterior and lateral tracts of the spinal cord. Demyelination of these neurons causes both peripheral and truncal weakness as well as paresthesias and a loss of vibration, pressure, and touch sensation. Progressive neurologic damage with untreated B12 deficiency includes spastic ataxia, anosmia, ageusia, and optic atrophy.4,20 Peripheral neuropathy may also be seen, and in those with diabetes, it can be difficult to distinguish from diabetic polyneuropathy.²¹ Finally, at its most severe, B12 deficiency may cause a dementia-like presentation termed “megaloblastic madness” with depression, mania, irritability, paranoia, delusions, and frank psychosis with hallucinations.^4,20 Clinicians need to be aware that concomitant anemia in the presence of neurologic signs may be absent in up to 20% of cases and delayed diagnosis can lead to progressive and irreversible damage.⁴

Diagnosis

Making the diagnosis of B12 deficiency requires attention to the limitations of current laboratory assays. Serum B12 levels are often the first test performed, however these are subject to both false negatives and false positives. A severely low level (<100 µg/mL) is often associated with signs and symptoms of deficiency. Significant variation exists between various laboratory assays and B12 levels may be spuriously normal or falsely high in patients with anti-intrinsic factor antibodies as intrinsic factor is often used in the U.S. as the assay-binding protein.²⁰ Thus, clinicians should consider the clinical context when interpreting serum levels and be careful to avoid direct comparison between two different values from independent laboratories (Table 2).

Elevated B12

An elevated serum B12 level is common. Prevalence ranges from 7-18% in hospitalized patients22 and does not necessarily exclude an underlying deficiency. The principle reason for a high level typically stems from an imbalance in B12 plasma binding proteins (haptocorrin, transcobalamin) related to either increased synthesis or decreased clearance. In liver disease, damaged hepatocytes release B12 in addition to abnormal hepatic clearance of haptocorrin. Elevated B12 levels may be seen in various solid and hematological cancers, mostly secondary to high haptocorrin production. Additionally, renal dysfunction leads to poor B12 clearance.^8,22

Methylmalonic Acid and Homocysteine

When clinical manifestations are subtle, measurement of serum methylmalonic acid (MMA) and homocysteine (HCys) can be helpful as they reflect key cellular pathways involving B12. Both MMA and HCys are elevated in >98% of patients with B12 deficiency; HCys will also be elevated in folate deficiency. Both levels decrease rapidly after treatment and can be used to ensure adequate B12 supplementation.²⁰ Limitations of MMA and HCys include falsely elevated levels in the presence of renal dysfunction.²⁰ variation in pregnancy without validated reference ranges,²⁴ and short-term fluctuations of MMA and HCys in both normal and deficient individuals.²⁵ There also is new evidence that polymorphisms in the gene HIBCH affect MMA levels irrespective of B12 status.²⁴

Determining Etiology

Identifying the cause of B12 deficiency aids in directing treatment. A detailed clinical history often reveals an obvious etiology such as vegetarian or vegan diets or patients with either gastric or ileal resections. The cumbersome Schilling test, involving administration of radioactive B12 and measuring fractional urine excretion, has been phased out. Non-invasive assessment for AIG currently relies on detection of serum autoantibodies to parietal cells (PCAs) and intrinsic factor (IFAs). The combination of PCA and IFA often improves the characteristics of this testing¹² (Table 3). However, the gold standard for diagnosis of AIG is endoscopy with biopsy. Elevated fasting serum gastrin and low serum pepsinogen may also be used to support diagnosis if uncertainty remains.¹⁴

Screening

No guidelines exist to assist clinicians with identification of patients at increased risk for deficiency and guide screening intervals. Nonetheless, clinicians should be aware of the high prevalence in certain key patient populations (Table 4). Expert opinion regarding several of these conditions suggests annual screening with a CBC and possibly serum B12, MMA, and HCys.

Management

Treatment of B12 deficiency has traditionally centered on increasing oral intake of food-bound B12 and intramuscular (IM) injection of the synthetic vitamin. Cyanocobalamin is the preferred form of B12 in the U.S., while hydroxocobalamin is primarily used in Europe; the latter formulation has been noted to have better retention and thus may be dosed less frequently.²⁴ Both are readily converted to the biologically active adenosylcobalamin and methylcobalamin.²⁴ Approximately 10-15% of a standard 1000µg IM B12 injection is retained, allowing for rapid replacement.^24,26 Guidelines from the British Society for Haematology recommend thrice weekly injections for two weeks in patients without neurologic deficits, with extension to three weeks or until clinical improvement if neurologic symptoms are present.² Injections may then be tapered to weekly for a month, then monthly in perpetuity if an irreversible cause is present. Improvement in MMA and HCys levels is seen within one-week; neurologic symptoms may take 6-12 weeks (sometimes with transient paradoxical worsening). Hematologic abnormalities may take up to eight weeks to normalize.^2,20

Oral replacement has become more popular in recent years given the cost, convenience, and pain associated with injection. For a similar 1000µg dose (as compared to IM), only 0.5-4% is absorbed.24 A Cochrane review of the available evidence found no difference between serum B12 levels in patients taking either IM or oral formulations (most commonly 1000µg/day). Outcomes related to signs and symptoms of deficiency or quality of life were not reported in the trials reviewed.26 Oral supplementation should ideally be administered in a fasting state as it is less effectively absorbed when taken with a meal.

Although there is some evidence for high dose oral supplementation in patients with known malabsorption or severe deficiency, most experts recommend IM administration. Treatment should be continued indefinitely if the etiology of malabsorption is irreversible – in patients with pernicious anemia who discontinue supplementation, neurologic symptoms recur as soon as 6 months; megaloblastic anemia can return within a few years.^24,27 A prophylactic daily oral dose of 1000µg B12 may be reasonable for patients having undergone bariatric surgery; in fact, this is recommended by the American Society for Metabolic and Bariatric Surgery.² Interestingly, despite the high prevalence in Crohn’s disease, the recent American College of Gastroenterology²⁸ and American Gastroenterology Association guidelines²⁹ do not address specific recommendations regarding B12 deficiency.

Other less common administration routes include sublingual³⁰ and intranasal,³¹ although the data supporting these modalities is derived from small cohorts of patients without severe clinical manifestations (or anemia in the sublingual cohort). There is anecdotal experience with successful subcutaneous (SQ) administration, however rigorous comparisons to IM have not been published. SQ injection is a preferred administration route by some patients at our institution, as they report less injection site pain as compared to IM. Table 5 provides a condensed summary of B12 repletion strategies.

CONCLUSION

B12 deficiency is common, yet under diagnosed, as clinical manifestations may be subtle. Serum B12 levels can be problematic and clinicians should consider obtaining MMA and HCys to assist with diagnosis. Treatment can prevent irreversible neurologic damage. Fortunately, there are many therapeutic options for treating B12 deficiency and maintaining adequate B12 reserves.

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Dispatches From The Guild Conference, Series #14

An Overview of Irritable Bowel Syndrome and its Relation to Small Intestinal Bacterial Overgrowth

July 2018 • Volume XLII, Issue 7

Priya Kathpalia,

Mark Pimentel

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Previously thought to be a diagnosis of exclusion, it is now clear that Irritable Bowel Syndrome (IBS) can be safely diagnosed at the time of an initial patient encounter by a gastroenterologist. Here we discuss the intimate relationship between small intestinal bacterial overgrowth (SIBO) and IBS and treatment options now targeted to reduce the bacterial load below a threshold that may cause symptoms. The pathophysiology of IBS based on alterations of the gut microbiome has taken a front seat in understanding this condition.

Irritable bowel syndrome (IBS) impacts a large proportion of our population and a large proportion of healthcare costs are attributed to this disease process. Previously thought to be a diagnosis of exclusion, it is now clear that IBS can be safely diagnosed at the time of an initial patient encounter by a gastroenterologist. Small intestinal bacterial overgrowth (SIBO) and IBS are intimately related and treatment options are now targeted to reduce the bacterial load below a threshold, which may cause symptoms. While the gut microbiome is complex, in 2018, the pathophysiology of IBS based on alterations of the gut microbiome has taken a front seat in understanding this condition.

Priya Kathpalia, MD¹ Mark Pimentel, MD, FRCP(C)^{2,3 1}Division of Gastroenterology, Center for Motility, University of California, San Francisco, CA ²Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA ³Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA

INTRODUCTION

UNDERSTANDING IMPACT OF DISEASE It is thought that irritable bowel syndrome (IBS) affects up to 45 million people in the United States alone and is more prevalent in females than in males.¹ Up to 40% of visits to the gastroenterologist are due to IBS symptoms. This disease causes significant burden to patients and their families alike, at times with symptoms so severe that their quality of life may be impaired. In addition, it is estimated that in the United States alone, direct healthcare costs due to IBS near $1 billion and another $50 million is attributed to indirect costs.²

IBS is characterized by alterations in bowel habits and associated abdominal discomfort. In particular, based on Rome IV criteria for the diagnosis of irritable syndrome, patients must have recurrent abdominal pain (not discomfort) weekly for at least 3 months and is associated with change in bowel habits (either stool form or frequency); symptoms must have started at least 6 months before establishing a diagnosis. Depending on the predominant bowel pattern type, there are various subtypes of the disease including IBS-D (diarrhea predominant), IBS-C (constipation predominant) or IBS-M (mixed diarrhea and constipation).³

Over the last 2 decades a number of theories have been proposed for IBS and have centered around the role of pain. However, evidence from this last decade has found that the microbiome may play a key role in symptoms in this condition. While various microbiome alterations have been described, one dominant theme is the finding of small intestinal bacterial overgrowth (SIBO) in a large subset of IBS. Studies suggest that this bacterial alteration could explain the majority of IBS patients, which is thought to be the prevailing etiology of IBS and is found in greater than 75% of IBS patients based on initial studies.⁴ In SIBO, the microbiome are altered such that the normally minimally colonized small bowel of humans now has an overabundance of non-pathogenic bacteria. The most accepted current definition is based on a recent North American consensus suggesting that coliform counts >103 cfu/mL define SIBO.⁵ Bacteria and their products in SIBO have the potential to produce bloating, abdominal pain and alterations in stool form and these symptoms are also typical of IBS.

SIBO and IBS: Are They Related?

Prior studies have suggested that >60% of patients with IBS-D in fact have a component of small intestinal bacterial overgrowth. This is based on breath testing and recent meta-analysis.⁶ While this had been controversial for many years, mounting evidence has shown the likelihood of small bowel bacteria causing IBS to be high. This is based now on data from intestinal culture,^7,8 deep sequencing9 and trials that demonstrate the benefits of the antibiotic, rifaximin.^10,11

While there is now a large body of evidence to support this, the reason for the SIBO in IBS remains incompletely understood. One of the main risk factors for the development of SIBO includes alterations in the migrating motor complex (MMC), or impaired motility of the GI tract. Stagnation of the gut will ultimately lead to a form of dysbiosis. This is reminiscent of classic forms of SIBO such as scleroderma or diabetes. However, in IBS there is growing evidence for the role of acute gastroenteritis in the development of IBS and SIBO. A large meta-analysis published in 2017 has now concluded that a major cause of IBS is acute gastroenteritis.¹² Based on animal studies, it is now believed that IBS and SIBO originate from this acute gastroenteritis.¹³ There is speculation that this transient food poisoning event or stressful stimulus permanently alters the MMC, and this stasis then serves as a nidus for bacterial overgrowth. Whenever considering SIBO, it is also important to rule out other causes besides IBS. Prior intra-abdominal surgical interventions, particularly those involving the ileocecal valve, are particularly notorious for precipitating SIBO in addition to prior mechanical obstructions, adhesive disease, and even Celiac or inflammatory bowel diseases (particularly in stricturing or fistulizing disease). Various immune and pancreatic exocrine deficiencies may be implicated as well. It should be noted that none of these risk factors may be present despite clinical suspicion of these conditions.

Dysbiosis and Constipation

It should be noted that previously SIBO was considered only in the setting of unexplained diarrhea, though if this were the case, it would be difficult to implicate intestinal dysbiosis in the pathogenesis of IBS, in which about half of patients present with constipation or mixed symptoms. With the initiation of breath testing, however, we have now recognized the association with methane producing organisms and constipation. In fact, prior studies have suggested a direct correlation with the degree of methane on breath testing with the severity of constipation experienced.¹⁴

In addition, the altered gut microbiome can also induce immune mediated cytokines that not only may precipitate dysmotility and augment nociceptive signaling and visceral hypersensitivity.¹⁵ As a result, it is thought SIBO is on the pathway to the development of IBS (Figure 1).

Testing: How to Come to the Diagnosis

Diagnosis requires comprehensive clinical history, a focused physical exam and depending on the type of IBS, laboratory, radiographic and endoscopic studies may also help aid in the diagnosis. IBS is no longer a diagnosis of exclusion but should be considered in the differential in a patient with altered bowel habits and associated abdominal pain.

A detailed history is essential in making the diagnosis of IBS. Physicians should look out for the so-called ‘alarm signs’ such as unintentional weight loss, symptoms that awake patients from their sleep, blood in stool, family history of colon cancer or onset of symptoms at an older age. Patients’ medications should also be reviewed as various agents may contribute to their symptoms. Surgical history and dietary habits should also be inquired.

Generally, IBS patients will have some abdominal tenderness with palpation but no other abnormalities are identified; if hepatosplenomegaly or ascites are noted, certainly other diagnoses should be considered. A digital rectal exam is essential before making the diagnosis of IBS as well to ensure no palpable masses, especially in patients with IBS-C.

The American College of Gastroenterology (ACG) guidelines suggest that in the absence of red flags, basic screening labs may not be needed be performed in patients with a new diagnosis of IBS at time of initial visit. However, there is some reassurance in negative studies and some studies that offer that reassurance include a complete blood count and thyroid studies. In patients with diarrhea predominant stools, Celiac disease serologies should also be performed although stool studies for common pathogenic bacteria, ova and parasites and inflammatory markers (serum erythrocyte sedimentation rates, C-reactive protein and/or fecal calprotectin) are less useful. As of 2016, new biomarkers for IBS-D and IBS-M have also been developed. There is an enzyme-linked immunosorbent assay (ELISA), which detects antibodies to cytolethal distending toxin B (CdtB); these antibodies have also been found to have cross-reactivity with vinculin, a protein in the intestine. This ELISA utilizing antibodies to both CdtB and vinculin is now commercially available and attempts to identify antibodies to the toxin which can be found as a result of food poisoning as well as autoantibodies to vinculin, hence its utility in post-infectious IBS patients with predominant diarrhea.¹⁶

In patients with red flag symptoms or in elderly patients, those having pain out of proportion to physical exam and those with sudden onset of symptoms or significant weight loss, further imaging should be considered. While endoscopic evaluation is not necessary prior to making the diagnosis of IBS, colonoscopy should be performed if there is a suspicion for inflammatory bowel disease and to exclude microscopic colitis (in the correct demographic such as over 50 years old with new onset of symptoms). All patients should be up to date with general colorectal cancer screening guidelines, and a sudden change in bowel habits without a clear precipitating factor, particularly in the elderly, should prompt colonoscopy.¹⁷

There is also a role for breath testing in patients with risk factors for SIBO, especially since there is >90% reproducibility of symptoms with lactulose or glucose substrates.¹⁸ This breath testing identifies both hydrogen and methane produced by the small intestinal bacteria; both of these innate gases are not traditionally made unless intestinal dysbiosis is present. The glucose substrate is particularly effective for diagnosing proximal SIBO where it is predominantly absorbed. Previously, small bowel aspirates were being obtained at the time of upper endoscopy but yield of SIBO is lower and the process of obtaining these samples has proven to be difficult both from implementation and cost perspectives.¹⁹

Medical Therapies: Understanding Current Treatment Options
Non-Pharmacologic Treatment Strategies

Treatments are largely aimed at reducing symptoms associated with IBS. Determining what to advise a patient really requires an individualized approach depending on their preferences and predominant symptoms. Non-pharmacologic techniques including adherence to a low-FODMAP diet are often recommended as first line therapy. However, recent data suggest extreme diets need supervision and may produce nutrient deficiencies.²⁰ Peppermint oil, probiotics, and various soluble fibers have also been suggested before considering prescription therapies. However, these have had limited success in small randomized controlled trials. In the case of probiotics, bloating may also be a side effect.²¹

Pharmacologic Treatment Strategies

As SIBO is thought to be a direct consequence of altered gut flora, it should be acknowledged that antibiotics may be an effective therapy for patients with this condition. Rifaximin, a non-absorbable antibiotic initially used for travelers’ diarrhea, has now proven to be beneficial in SIBO patients and has been approved by the Food and Drug Administration (FDA) for IBS-D. Neomycin and metronidazole, though not FDA approved for this indication, have been shown to be beneficial when added to patients with methane predominant SIBO in those with underlying IBS-C and reduction in methane may in fact treat the constipation as well.

In addition, patients must understand that if there is truly a component of intestinal dysbiosis, symptoms will certainly improve but will not resolve entirely. However, in the TARGET 3 trial 36% of subjects who responded to rifaximin did not need any further treatment. Nevertheless, relapse of symptoms can be seen in many patients who initially respond to rifaximin.²² In patients who had clinical evidence of IBS and abnormal hydrogen breath testing using a glucose substrate, treatment with rifaximin resulted in normalization in breath testing; however, >40% patients had recurrence of symptoms 9 months after the initial course of rifaximin and again abnormal breath testing.²² Thus it is reasonable to conclude that the degree of small intestinal bacteria re-accumulation correlates with degree of symptoms. Use of a pro-kinetic such as erythromycin, at low nocturnal dosages, after successful treatment of IBS with an antibiotic delayed relapse of SIBO from 59 to 138 days;²³ it is interesting to recognize that at low dosages, erythromycin does not exhibit antimicrobial properties but can be useful in stimulating the MMC.²³

Aside from antibiotics, other FDA-approved drugs for IBS-D include eluxadoline (mu-opioid agonist) and alosetron (5-HT3 antagonist), the latter approved for women in particular. It should be noted that alosetron has the rare but reported risk of ischemic colitis and in fact inducing severe constipation. Bile acid sequestrants and anti-diarrheal agents (lomotil, loperamide), though not FDA approved, work in a small proportion of patients with IBS-D and thus are often tried in addition to and in conjunction with the above therapies. For IBS-C, lubiprostone (intestinal chloride channel activator) and linaclotide (cyclic guanosine monophosphate [cGMP] activator) are FDA approved therapies.

Given the gut-brain connection, various studies have also demonstrated effectiveness of tricyclic antidepressants, selective serotonin receptor inhibitors (SSRIs) and selective serotonin and norepinephrine receptor inhibitors (SNRIs) in the treatment of IBS whereby pain is the predominant symptom. However, these drugs are not FDA-approved for this indication.

SUMMARY

Irritable bowel syndrome is a complex disease process and no longer considered a diagnosis of exclusion. It is thought that small intestinal bacterial overgrowth plays an important role in the pathogenesis of IBS and the intestinal dysbiosis may precipitate symptoms such as visceral hypersensitivity due to nociceptive stimulus. In the presence of ‘alarm’ symptoms such as unintentional weight loss, blood in stool, or sudden onset in symptoms, further work up may be warranted and entails a combination of laboratory, radiologic, and endoscopic testing. Treatment options are aimed at targeting the prevailing symptom in IBS, but further research is required to treat the underlying etiology now that the pathophysiology of the disease has been definitively established.

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Nutrition Issues In Gastroenterology, Series #175

When a Registered Dietitian Becomes the Patient – Translating the Science of the Low FODMAP Diet to Daily Living

May 2018 • Volume XLII, Issue 5

Wendy Phillips,

Janelle Walker

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Irritable Bowel Syndrome (IBS) can severely affect quality of life due to abdominal pain, bloating, diarrhea and/or constipation. Symptoms can be improved by following a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), but implementation of this restrictive diet can be challenging. This article provides guidance for all 3 phases of the low FODMAP diet from an IBS patient, who utilized her knowledge as a registered dietitian nutritionist to successfully resolve symptoms, discontinue IBS-related medications, and maintain a nutritionally complete diet.

Wendy Phillips, MS, RD, CNSC, CLE, FAND, Division Director of Clinical Nutrition, Morrison Healthcare, St. George, UT Janelle Walker, MBA, CLE, Lifestyle Educator, Kaiser Permanente, Bakersfield, CA

INTRODUCTION

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder that can severely affect quality of life due to abdominal pain, bloating, diarrhea, and/or constipation.^1,2The pathophysiology is complex and multifactorial, including visceral hypersensitivity3, alterations in the GI microbiome,^4-8 and psychosocial factors including the brain-gut axis.9 Often, IBS is not diagnosed until other causes for symptoms have been ruled out, such as cancer, infectious colitis, inflammatory bowel disease, or celiac disease.10 Since the pathophysiology of IBS is multifactorial, more than one treatment method is often used, including medication management of symptoms, stress management including biofeedback, and dietary intervention.^1,2 This article focuses specifically on the implementation of a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, which has been shown to reduce symptoms in those with IBS and is included in the National Institute for Health and Care Excellence Clinical Guidelines for IBS.²

IBS is divided into four categories: IBS-D (IBS with diarrhea), IBS-C (IBS with constipation), IBS-M (IBS with mixed symptoms), and IBS-U (IBS un-subtyped). The Rome IV criteria is used to determine the type of IBS based on abdominal pain and stool consistency; this classification is then used to guide treatment.¹¹ The Gastrointestinal Symptom Rating Scale (GSRS) is a symptom assessment tool that measures the baseline severity and frequency of these symptoms, as well as the response to treatment. It has been validated for both clinical and research application in patients with IBS.¹² Many trials evaluating dietary interventions for IBS, such as the low FODMAP diet, use the GSRS to assess symptom change.

Treatment goals are typically designed to match the outcome measures used in these studies, such as the GSRS. This is important for diet standardization to determine which foods have the highest likelihood of inducing symptoms. Beyond that, each individual patient should determine goals for their own therapy. For example, one patient may focus most on reducing frequency or urgency of diarrhea, while another patient may prioritize reduction in abdominal pain and bloating. Oftentimes, treating one symptom also helps alleviate others, but patients need to stay focused on a “what’s in it for them” framework in order to maintain adequate motivation and adhere to such a restrictive diet. Examples of patient-centered goals are listed in Table 1.

Dietary Intervention for IBS – The Low FODMAP Diet

In a recent survey of 1,562 U.S. GI physicians, nearly 60% indicated that at least half of their patients with IBS associate food with their GI symptoms. Prior to seeking treatment with a GI specialist patients were more likely to use ‘trial and error’, or a lactose-free or gluten-free diet rather than trying a low FODMAP diet.¹³ Over half of the GI physicians recommended diet therapy to > 75% of their patients with IBS with the low FODMAP diet being the most common.

For many individuals, foods that contain FODMAPs (all of which are carbohydrates), have been shown to exacerbate IBS.^14-16 Consuming a diet that restricts foods with high levels of FODMAPs has been shown to reduce symptoms and therefore improve quality of life in 50-80% of patients with IBS.^17-25 FODMAPs are highly osmotic (draw water into the gut), poorly absorbed, and are rapidly fermented by intestinal bacteria resulting in excess gas production.

FODMAP rich foods are categorized into those containing fructans/galacto-oligosaccharides (GOS), lactose, excess fructose (fructose to glucose ratio > 1), and polyols. Some foods may contain more than one category. Table 2 provides resources to help identify foods in each category.

Fructans and Galacto-oligosaccharides (GOS)

Fructans are fructose polymers (oligosaccharides) that are found in many foods, including onions, garlic, and some fruits and cereals. Also included in this category are inulin and fructo-oligosaccharides that are added to many foods as prebiotics. The small bowel (SB) cannot hydrolyze the fructose-fructose bonds, so fructans enters the colon instead of being absorbed in the SB.²⁶ In the colon they are fermented by colonic bacteria, causing the symptoms associated with IBS in those with visceral hypersensitivity. Wheat, onions, and garlic are fructans that are highly prevalent in the U.S. food supply. GOS molecules consist of galactose-galactose bonds that also cannot be hydrolyzed or absorbed in the SB, causing similar symptoms as fructans in the colon. Lentils, chickpeas (and therefore hummus), and red kidney beans are common sources of GOS.

Lactose

Many individuals, even those that do not have IBS, are lactose intolerant or lactose maldigesters.²⁷ Lactose is a disaccharide of glucose and galactose, normally hydrolyzed in the brush border of the proximal SB. When lactose is malabsorbed, the disaccharide can cause gas production and distension in both the SB and colon. Common sources of lactose include milk, ice cream/cream, yogurt, and some cheeses.

Fructose

Fructose is more readily absorbed in the SB in the presence of glucose, so foods with excess fructose compared to glucose will lead to fructose malabsorption.²⁶ Individuals with IBS and visceral hypersensitivity will have abdominal distension, pain, and bloating in response to this fructose malabsorption. Foods with excess fructose content include, but are not limited to, watermelon, pineapple, honey, apples, pears, and all foods and beverages with high fructose corn syrup.

Polyols

Polyols are reduced calorie/carbohydrate sweeteners,²⁸ commonly known as sugar alcohols (such as sorbitol, mannitol, xylitol, isomalt). Sorbitol and mannitol are naturally occurring in foods like mushrooms, avocadoes, prunes/prune juice, and stone fruits, but are also added to sugar-free foods such as gelatin, pudding, and beverages. Xylitol and isomalt are added to commercially sweetened products such as chewing gums and products marketed as “sugar-free.” These polyols are slowly absorbed along the length of the SB. They often reach the colon where they act as osmotic agents pulling fluid into the bowel in addition to being fermented by colonic bacteria. This causes the ‘bloating and distension’ that is common in IBS. All individuals, not just those with IBS, are susceptible to diarrhea when consuming these products in high amounts, thus the warnings on many products containing artificially added sugar alcohols – “excess consumption may have a laxative effect.” Individuals with IBS may have a lower threshold for reacting to polyols.²⁸

FODMAP Diet Implementation

Although implementation of the low FODMAP diet can be challenging, the survey of GI physicians indicated that only 21% of gastroenterologists commonly refer patients with IBS to a registered dietitian nutritionist (RDN), indicating a need for improved interdisciplinary care of these patients.¹³ A RDN should complete a nutrition assessment and develop a nutrition care plan to help the patient and significant others plan a successful low FODMAP diet. The RDN should first conduct an anthropometric and diet history. Some patients with IBS may perceive themselves as overweight or have body dissatisfaction due to the frequent bloating associated with eating. The RDN should work with the patient to establish a healthy and reasonable weight goal, if needed. A food frequency questionnaire can be a helpful diet history tool, as this will highlight foods or food groups that are already avoided due to known symptom induction, intolerances, or allergies. It will be important to note which foods are regularly consumed that are high in FODMAPS, suggesting alternative food choices for these.

The RDN should also investigate lifestyle factors such as stress, physical activity, and social/environmental situations to determine impact on symptoms and ability to implement the 3 phases of the diet. Baseline food-related knowledge can be built upon to teach the diet specifics and food label reading. The planned diet should be consistent with the patient’s beliefs associated with food, whether cultural, religious, ethnic, or for other reasons. Additionally, confirmed or suspected food allergies or intolerances need to be considered during diet planning.

Documenting current and historical medications, including frequency and dosage, can provide insight into symptom longevity, severity, and frequency. It is important to note that some medications may contain FODMAPs as fillers or sweeteners. The ability to reduce or discontinue medications while achieving symptomatic improvement will be a measure of the FODMAP-modified diet success for most patients.

FODMAP Diet Phases

After a nutrition assessment has been completed and goals for treatment have been set, diet implementation follows. The diet is broken into 3 phases (see Table 3). Phase 1 is the Restriction Phase, Phase 2 is the Reintroduction Phase, and Phase 3 is the Maintenance Phase.

Phase 1. Restriction

In Phase 1, all foods high in FODMAPs are restricted completely, and foods with moderate levels of FODMAPs are limited to small portions. The cut-off level for what is considered low, moderate, or high FODMAP content is not well defined; therefore, food restrictions may differ based on the individual’s threshold response and can be fine-tuned throughout the Restriction Phase.²⁹ Tables 4 and 5 provide commonly eaten foods in each FODMAP category, but this is not an exhaustive list. Monash University and other groups periodically retest foods as changes in agriculture and the environment can influence the FODMAP levels in food and food analysis techniques become more sophisticated and accurate over time.³⁰ For example, Monash University retested bananas because many people reported discomfort after eating ripe bananas. Also, fruits available in grocery stores may be larger than in the past, influencing the total fructose content. This is why food and symptom logs (see Table 4) can be helpful to identify exactly which foods in which quantities are the most likely to trigger symptoms in an individual person.

Viewing lists of high and moderate FODMAP foods can be overwhelming to an individual with IBS who is learning this diet for the first time. Table 5 provides a chart that can be used for the RDN and patient to complete together, identifying commonly eaten foods from the FODMAP food lists (from the resources in Table 2) that should be avoided completely, eaten in small portions, or eaten in the usual portion sizes. This can also help the individual focus more on what they can eat, not what they cannot eat.

This Restriction Phase should be maintained for 2-6 weeks to determine if it will be effective for symptom reduction, as many people will see significant symptom improvement by week 2, while others may require a longer period of complete FODMAP restriction.10 If symptoms have not improved by week 6, then it is unlikely that the diet will be effective. In this case, a return to the previous/usual diet is warranted with new treatment modalities pursued, such as stress or medication management. If symptoms have improved by week 4, the patient should start the Reintroduction Phase rather than waiting the full 6 weeks. The goal is to increase diet variety as much as possible to ensure compliance and reduce the risks of nutrient deficiencies that may come with prolonged restriction. This is especially important because Phase 1 of the low FODMAP diet limits many common food sources of fiber, vitamin D, and calcium.

Compliance with Phase 1 can be even more difficult if traveling or eating in social situations. Packing FODMAP friendly snacks and ingredients that are easy to prepare when traveling can be helpful. Table 6 provides examples of simple meals that are consistent with a low FODMAP diet. RDNs can also help IBS patients learn how to read food labels for packaged foods that are available in airports and convenience stores.

Many find it helpful to document their intake on a food and symptom log such as that in Table 4 to monitor their own compliance and more easily track intermittent symptoms back to specific foods. Also, since food analyses can be updated, maintaining a log may facilitate decision-making on which foods should be limited in the future. For example, symptoms may be associated with a meal in which no moderate or high FODMAP foods were eaten. Future food analysis may then identify one of those foods with higher FODMAP content than originally thought. The food and symptom log can be used to identify foods that may need to be avoided based on the new analysis.

Phase 2. Reintroduction
No randomized control trials exist to guide the Reintroduction and Maintenance phases of the diet; Whelan and colleagues published guidance based on limited research and best practices followed in their center.¹⁰ The resources listed in Table 2 are also helpful for Phase 2. This article includes additional guidance using the author’s experience as both a RDN and IBS patient. Tips for reintroducing foods are included in Table 7.
Patients may be fearful of inducing symptoms with food reintroduction. However, in order to avoid unnecessary restriction and promote a nutrient-complete, more enjoyable diet, as many foods as possible need to be reintroduced over time.
At the beginning of the Reintroduction Phase a second nutrition assessment with an RDN is helpful to evaluate anthropometric and clinical changes and progress towards the patient-centered care goals. A revision of the goals at this point may be necessary. A new food frequency questionnaire can be completed to determine compliance with the Restriction Phase and identify key nutrient intakes that may be at risk. For example, if the individual has not been consuming calcium-fortified products or cheese, and has maintained a strict dairy restriction as recommended, he/she may require calcium and vitamin D supplementation. Therefore, if lactose intolerance has not been confirmed, the first category of foods to be reintroduced should be lactose containing foods. Yogurt is a good choice as it is often better tolerated than milk or ice cream.
One new food from only one new food category should be reintroduced every 3 days during a food challenge, while continuing to restrict other foods. A food from a new category should be chosen for each food challenge, as people will often respond similarly to foods in the same category. For example, both wheat and onions are in the fructan category, so a person with IBS who responds poorly to wheat will probably have a similar reaction to onions and other fructan-containing foods. Dose dependent reactions may occur,²⁹ so smaller-than-usual portion sizes should be trialed on day 1 of a food challenge. For example, if wheat is being reintroduced, 1/2 slice of bread may be eaten on day 1, increasing to a full slice on day 2 and then 2 slices on day 3 if still asymptomatic.
Some foods fit in more than 1 category, such as apples in both the polyols and excess fructose groups. These foods are not good choices for the first round of food challenges, as it will be too difficult to discern which category of foods is responsible for symptoms. A return to a full restriction for 3 days between food challenges can help ensure symptoms are not a result of overlap between food categories. The following pattern is suggested for the first round of food challenges:
2-6 week full FODMAP restriction
3 day food challenge – small servings of wheat reintroduced (fructan)
3 day full FODMAP restriction
3 day food challenge – small servings of yogurt reintroduced (lactose)
3 day full FODMAP restriction
3 day food challenge – small servings mushrooms reintroduced (polyols)
3 day full FODMAP restriction
3 day food challenge – small servings of honey reintroduced (excess fructose)
All foods successfully reintroduced can now be continued in normal serving sizes. New 3-day food challenges could be implemented with new foods, without needing to repeat periodic full FODMAP restrictions, since all FODMAP categories have been trialed.

Maintenance Phase

Most people with IBS will remain in this phase for the rest of their life to continue symptom-free. Good compliance with the diet has been reported due to symptom resolution when the diet is followed, improving quality of life.31 The ultimate goal is to consume as many different foods as possible in order to meet nutrient requirements. If some foods produce mild symptoms, these may still be eaten in small amounts on special occasions if so desired. For example, those with IBS who are sensitive to fructan-containing foods may choose to eat small portions of bakery goods made with wheat flour at a celebration.

Many choose to return to the guidance provided in the Reintroduction Phase to retry foods previously not tolerated, especially if they are favorite foods. The lifetime FODMAP modified diet can be continually refined, especially as new treatment strategies are advanced.

Additional Considerations

Liquid medications, such as cough syrups and pain relievers, contain high fructose corn syrup and sugar alcohols (polyols) as well as other FODMAP components. Individuals with IBS should consult with their physicians and pharmacists for alternate medication selections if needed.

A sustained low FODMAP diet may alter the gut microbiota due to reduced intake of inulin and GOS, the fructans that are natural prebiotics.^4-8 It is difficult to know the long term consequences of this alteration, because only short term studies have been done to elucidate this effect.¹⁰ Other dietary modifications may also contribute to changes in the microbiome. One randomized control trial demonstrated beneficial microbiota alterations when probiotics were consumed concurrently with the FODMAP modified diet.⁸ Since more research needs to be done on the type and dose of probiotics that might be beneficial, individuals with IBS should discuss possible probiotic supplementation with their gastroenterologist and/or primary care physician.

CONCLUSION

A FODMAP modified diet has been shown to improve IBS symptoms. With careful planning this diet can be nutritionally complete. Significant improvement in the quality of life for those suffering from IBS may promote diet compliance. Gastroenterologists should refer patients with IBS to a RDN for nutrition assessment, education, and diet planning.

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Nutrition Issues In Gastroenterology, Series #174

Nutritional Care of the Patient with Eosinophilic Esophagitis

April 2018 • Volume XLII, Issue 4

Raquel Durban,

Evan S. Dellon

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Dietary elimination is an effective treatment for initial and long-term management of EoE. However, with the elimination of food groups, concerns arise for nutritional risk and quality of life. In this article we discuss the importance of providing patients with resources and education to teach food avoidance techniques on the prescribed elimination diet, as well as strategies to implement a diet that is allergen free, nutritionally dense, and diverse enough to maintain adherence, nutrition status and QoL. Successful EoE treatment with dietary modification requires a multidisciplinary approach, with gastroenterologists, allergists and dietitians.

Eosinophilic Esophagitis (EoE) is a chronic allergic disease that is characterized by esophageal inflammation and dysfunction. The symptoms vary by age and represent a spectrum from growth failure, vomiting, abdominal pain, and heartburn in children, to dysphagia and food impaction in adolescents and adults. EoE can be treated with dietary elimination, swallowed topical corticosteroids, and, in cases where there are esophageal strictures, dilation. Dietary elimination is the strategic removal of food antigens felt to trigger disease activity. With the elimination of food groups, concerns arise for nutritional risk. Education should be provided to teach techniques on food antigen avoidance as well as strategies to implement a diet that is nutritionally dense, diverse enough to maintain adherence and ensures adequate growth and nutrition status.

Raquel Durban, RD, Asthma and Allergy Specialists Evan S. Dellon, MD MPH, Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine Chapel Hill, NC

INTRODUCTION AND EOSINOPHILIC ESOPHAGITIS OVERVIEW

Eosinophilic Esophagitis (EoE) is a chronic allergic disease that is characterized histologically by eosinophil-predominate esophageal inflammation and clinically by symptoms of esophageal dysfunction that vary by age.¹ The most recent prevalence data demonstrates 56.7/100,000 persons with EoE in the United States, affecting all ages;² both incidence and prevalence of EoE are rapidly increasing.³ In infants and toddlers, symptoms may include growth failure and feeding difficulties. In elementary school-aged children, symptoms are typically abdominal pain, vomiting, heartburn or regurgitation. In adolescents and adults, dysphagia and food impaction predominate.⁴ (Table 1). Consensus recommendations provide guidelines on diagnosis and treatment of EoE.^5-6 Diagnosis is based on symptoms of esophageal dysfunction, esophageal biopsy with eosinophil predominate inflammation of ≥ 15 eosinophils per high power field (eos/hpf), and persistence of eosinophils isolated to the esophagus after a trial of proton pump inhibitors (PPI) in the absence of secondary causes of eosinophilia.¹ However, these diagnostic criteria have been under debate recently, and European guidelines from 2017 have suggested that failure of response to a PPI be eliminated as a diagnostic criterion.⁷ This suggestion is largely based on observations that patients with EoE who do and do not respond to PPI treatment share many similar clinical, endoscopic, histologic, immunologic, and molecular characteristics.^8-9 There are three general treatment approaches for EoE: dietary elimination, pharmacotherapy, or, in cases of esophageal strictures, dilation.¹ When considering the optimal treatment method, an individualized plan of care should consider medical, nutritional, and practical barriers to adherence, and a shared decision-making framework should be used to select a therapy.¹⁰ There are currently no FDA-approved medications to treat EoE. However, it has been demonstrated that off label use of topical corticosteroids, when swallowed, effectively treat EoE.^11,12 Specifically, asthma steroid preparations can be swallowed rather than inhaled to coat the esophagus and provide an anti- inflammatory effect. This approach is effective in many patients,¹³ and formulations of topical steroids are under commercial development.^14,15 However, a downside of these medications is that when they are stopped, symptoms quickly recur, and long-term maintenance therapy is required.¹⁶ Non-pharmacologic therapies might therefore be desirable.

Dietary Treatment of EoEand Nutritional Implications

Dietary management strategies have been discussed extensively by Groetch et al. in the 2017 Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report from the American Academy of Allergy, Asthma and Immunology (AAAAI).¹⁷ The overall concept is to identify and remove food allergy triggers of EoE from the diet. To do this, dietary elimination is managed with one of three options: elemental formula, empiric dietary elimination, and test- directed dietary modification. While an elemental diet is the most effective of the dietary elimination options in inducing remission with response rates above 90%, it is also the most restrictive of the diets.^8-21 Patients following an elemental diet are only allowed to consume amino acid based formula (AAF) (Table 2), and a few non-nutritious treats (Table 3). There are several available choices of AAF, each with unique macronutrient and micronutrient content, so it is crucial that attention be given to specific formula selection. Use of an elemental diet in young children may impede development of feeding skills.²² Due to the volume required to meet nutritional requirements, some patients may require a feeding tube for formula administration. Patients on an elemental diet also have prolonged food reintroduction periods to reach a stable diet and may experience social isolation.¹⁷ Finally, expense can be prohibitive, as only a minority of states offer insurance coverage for AAFs, so patients must work with their physicians to explore coverage options. Because of the restrictive nature of elemental diets, empiric elimination diets were developed as these were easier to adhere to, but still achieved good efficacy, typically in the 60-70% range. The initial empiric elimination diet, which is still the standard, was the so-called six-food elimination diet (SFED), where the “top six” allergens were eliminated (dairy, wheat, egg, soy, nuts, and seafood). SFED has been shown to be effective in adults²³ and children²⁴ Nevertheless, this diet is still quite restrictive, so newer iterations have tested empiric elimination of one food (dairy),²⁵ four foods (dairy, wheat, egg, soy),^26,27 or most recently a “step- up” approach where two foods (dairy and wheat) are eliminated initially, followed by four and then six food groups, depending on patient response.²⁸ Studies demonstrate histological and symptom improvement; however, they lack consistency in their specific food group eliminations and efficacy rates in adults and pediatrics. The Consortium for Eosinophilic Gastrointestinal Researchers, an NIH- funded multicenter research network, includes the food groups outlined in Table 4 when conducting empiric diet elimination efficacy studies. Allergy test-directed diets eliminate foods based on the interpretation of skin prick testing (SPT) and/or atopy patch testing (APT), but these are the least effective option, with response rates in the 40% range.²⁰ Because of this, the updated Food Allergy Practice Parameters²⁹ report that IgE blood testing, and SPT and APT alone are not sufficient to diagnose food triggers of EoE. In addition to being the least effective treatment modality, testing for directed diets can be cumbersome,³⁰ as APT requires small metal disks to be affixed to the patient’s skin for 48 hours and a return visit for result interpretation at 72 hours. As well, SPT may cause localized discomfort. Test direct elimination diets may result in the removal of foods not recognized by the allergen labeling laws, thus increasing the risk for accidental allergen exposure due to difficulty in identifying the allergen within ingredient list. With any elimination diet, dietary education is necessary to ensure adequate nutrition and reduce the risk of accidental allergen ingestion while maintaining quality of life (QoL). Dietary elimination education must consider a patient’s current nutritional status and ensure effective development of individualized strategies to aid in diet prescription adherence. Note that after a patient achieves remission of EoE based on histological reevaluation using dietary elimination, education is also important for food reintroduction. Enlisting consultation with a registered dietitian should also be considered for patients experiencing treatment failure due to poor adherence, unintentional weight changes, unbalanced diet or factors related to QoL.¹⁷ INDANA, the International Network for Diet and Nutrition in Allergy, http://www. indana-allergynetwork.org/, can aid in locating a registered dietitian savvy in dietary elimination related to food allergy or EoE. There are also many available tools and further guidance in the AAAAI Workgroup Report on Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis.¹⁷ Education provided will guide the patient to shop and purchase allergen free and nutritionally appropriate foods independent of the health care provider. This is particularly important, as prior research has shown that the cost of elimination diets and specialty foods is not negligible.³¹ Label reading education is also crucial, and has two key components, the ingredient panel and the precautionary allergen labels (PAL). The ingredient panel is regulated by the United States Food Allergen Labeling and Consumer Protection Act (FALCPA) and requires that the top 8 most common food allergens in the United States (cow’s milk, wheat, egg, soy, peanut, tree nut, shellfish and fish) be labeled by its common name in a clear and distinct fashion. Soy and peanut oil (highly refined oils), as well as soy lecithin32 are allowable ingredients. While FALCPA is beneficial for patients following an empiric elimination diet, which encompasses only these foods, test directed diets may eliminate foods outside of the scope of FALCPA and may increase potential for accidental allergen exposure. Other ingredients may have unknown origins such as “natural flavorings” or “modified food starch” and it may be helpful to contact the manufacturer for ingredient source details. PAL statements indicate the possibility of a product containing an allergen due to inadvertent cross contact during the manufacturing process. These statements are not regulated in their verbiage and are voluntary in placement. Table 5 provides an example of the differences in FALCPA and PAL label statements. Threshold levels of exposure to allergens in EoE are currently not known, but accepted management practice suggests avoidance of allergens as well as potential sources of cross contamination.¹⁷ Once allergen avoidance techniques have been learned, discussing implementation of the rules into daily practice should be completed. While the ultimate goals are to improve histology and symptoms, as well as to ensure QoL and nutrition, the diet does not have to be implemented immediately or all at once, and patients and families can transition into a diet over a few weeks’ time. During these weeks, patients can build a list of foods and supplies that need to be substituted. For example, milk and milk-based ingredients are a ubiquitous staple of the American diet, and a palatable yet nutritionally appropriate substitution may require trialing a variety of alternative milks (Table 6), cheeses and yogurts. An extensive nutritional comparison of available milk alternatives has recently been published.³³ Each eliminated food group contributes to a balanced diet and care must be taken during replacement selection. Table 7 provides suggestions on allergen replacements to use while cooking. It is important to note that children under the age of two, who are not breastfed and who are required to avoid cow’s milk should be prescribed an AAF.³⁴ A two-day sample menu is available in Table 8, and additional materials are available in the AAAAI Work Group Report.¹⁷ After the first phase of an elimination diet has been successfully completed with histological remission, reintroduction of foods may be considered by the care team. The recommendation is to reintroduce only one food or food group back into the diet at a time and wait six weeks¹⁷ before conducting a repeat endoscopy to verify the EoE remains in remission.^26,27 In patients with known IgE-type immediate allergic reactions to food, it is also important to collaborate with an allergist during the food reintroduction phase to minimize the likelihood of IgE-mediated reactions. There is no set protocol for food reintroduction, though many providers add back the least allergenic food, or the food least likely to trigger EoE, first. Selection of a food to reintroduce should also consider the patient’s ability to eat. Children, in particular, may have delays in oral motor development, adaptive behaviors, or require texture modification. Collaboration with a feeding therapist may be beneficial to diet expansion.¹⁷ Throughout dietary elimination phases, the patient should be monitored to ensure adequate nutrition and/or growth as well as address barriers to adherence. Monitoring methods include tracking anthropometrics and review of patient’s dietary recall to identify allergen and nutrition risks while assessing quality of life. If nutritional risks are identified, laboratory tests may be valuable.17

CONCLUSIONS

Dietary elimination is an effective treatment for initial and long-term management of EoE.^24,35 However, with the elimination of food groups, concerns arise for nutritional risk and quality of life. Education and resources (Table 9) should be provided to teach food avoidance techniques on the prescribed elimination diet, as well as strategies to implement a diet that is allergen free, nutritionally dense, and diverse enough to maintain adherence, nutrition status and QoL. Successful EoE treatment with dietary modification requires a multidisciplinary approach, with gastroenterologists, allergists and dietitians.

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Nutrition Issues In Gastroenterology, Series #171

Moo-ove Over, Cow’s Milk – The Rise of Plant-Based Dairy Alternatives

January 2018 • Volume XLII, Issue 1

Meagan Bridges

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Consumer demand for alternatives to dairy is on the rise, and with it, an ever-expanding array of plant-based products from which to choose. This is especially evident when considering milk substitutes. Each type of non-dairy milk offers a unique nutritional profile, with a wide range of values for protein, carbohydrates and fat, along with vitamins and minerals. In this article, we review which non-dairy beverages are gaining in popularity and how these options compare nutritionally to cow’s milk.

The Rise of Plant-Based Milks

When choosing milk, it is no longer simply a matter of whole, low-fat, or skim. Now more than ever, consumers can choose from a plethora of plant-based “milks” derived from a variety of sources, including nuts, seeds, legumes, and cereal grains.

Worldwide sales of non-dairy milk alternatives more than doubled between 2009 and 2015, reaching $21 billion – a reflection of both consumer demand and the burgeoning array of products to meet that demand. Meanwhile, consumption of cow’s milk has dropped 13 percent in the U.S. over the last five years.¹

Plant-based milk substitutes are essentially suspensions of dissolved and disintegrated plant material and extracts in water. Homogenization and thermal treatments are used to improve the suspension and stability of the product. They are made to visually resemble cow’s milk and often include the word “milk” in the beverage name. Specific nutritional properties depend on the plant source, processing, and fortification. The most widely available plant-based milks in the U.S. are identified in Table 1.

The increasing popularity of non-dairy milks can be attributed to many factors. More and more people are consuming non-dairy alternatives, whether due to an allergy, lactose intolerance or adherence to a vegan/plant-based diet. Still others are concerned over saturated fat levels, hormone content, and antibiotic use in dairy cattle. But with an ever expanding array of options, the dairy aisle can end up being a place of utter confusion, especially when weighing not only taste, texture, and other sensory attributes of non-dairy milks, but also the nutritional qualities of these beverages and how they compare to cow’s milk.

How Do Plant-Based Milks Compare to Cow’s Milk?

Dairy foods are often good sources of important nutrients, including protein, vitamin D, calcium, and phosphorus. As some plant-based milks are very low in these nutrients, consumer awareness is important when dairy-free alternatives are used as a direct replacement for cow’s milk in the diet. For example, of all the non-dairy alternatives, only soy milk naturally contains protein in an amount comparable to cow’s milk (8 g per 8 oz. cup). By contrast, almond milk – one of the most popular non-dairy options among consumers – only contains 1 g of protein per 8 oz. cup.

Moreover, every gram of protein is not created equally, and it is important to evaluate the quality of protein when comparing plant-based milks to cow’s milk. Protein quality is based on amino acid composition, digestibility, bioavailability, and specific protein-derived components. Protein from animal sources is generally of higher quality than plant-based protein due to its more “complete” array of amino acids.² Cow’s milk contains both whey and casein proteins, which have high biological value given their “usability” by the body. While soy protein is also recognized for its high biological value among plant sources, its usability when derived from soy milk has not been extensively studied.³ Most other proteins found in plant-based milks are not complete and do not offer the full array of essential amino acids.

While non-dairy alternatives do not offer exact nutritional equivalency to cow’s milk, they can be fortified with certain nutrients – especially calcium, vitamin D, and vitamin B12 – to make them more comparable. In fact, many fortified plant-based milks are marketed as having equal or greater amounts of calcium and vitamin D than cow’s milk. However, it is important to recognize that the bioavailability of such nutrients varies significantly among products and in many cases is not precisely known.³

By the same token, while the quantity of most micronutrients has been established for cow’s milk, similar information is not available for most non-dairy beverages. In fact, only figures for calcium and vitamin D are consistently reported for non-dairy milks on the USDA’s Food Composition Databases; figures on phosphorus, zinc, thiamin, niacin, vitamin B6, folate, vitamin E, vitamin K, and other micronutrients are often missing.⁴ Table 2, which compares the nutritional profile of popular plant-based milks to 2% cow’s milk, omits these particular vitamins and minerals, as most of this information is not yet readily available.

In addition to protein and vitamin/mineral content, added sugar is another variable that can vary widely among plant-based milks and depart drastically from cow’s milk. While unsweetened versions have as few as 25 calories per cup, most non-dairy milks are sweetened with added sugars (such as rice syrup, barley malt, or cane sugar) to make them more palatable. Many sweetened and/ or flavored non-dairy milks contain up to 20 g of sugar, compared to 12.5 g of naturally occurring lactose in 2% cow’s milk.

Finally, consumers should be aware of any additives used to emulsify and stabilize plant- based milks. Some leading nut milks, for example, contain carrageenan, a thickener and emulsifier derived from seaweed that has recently been implicated in some preliminary (though far from conclusive) studies on ulcers, inflammation, and other GI complications. Other non-dairy milks can be thickened with sunflower lecithin or a variety of gums. Learn more about the specific properties of the most popular plant-based milks below.

Soy Milk

Likely the most recognizable among dairy-free alternatives, soy milk is the “original” replacement for cow’s milk, first appearing on shelves in the U.S. in the 1950s. Made by soaking, crushing, cooking, and straining soybeans, it is the only milk alternative that naturally contains the same amount of protein as a cup of cow’s milk – 8 grams – along with omega-3 fatty acids and fiber. Most manufacturers also fortify soy milk with vitamins A, D, B12, and calcium. In addition, soy milk can be a good source of manganese and magnesium.

Interestingly, when considering the manufacturing process, soy milk is likely the “least processed” out of all plant-based milks. At the same time, soy is one of the top three genetically modified organisms (GMOs) in the U.S., with 94% of all soybeans in the country being genetically engineered.⁵ Most mainstream brands, however, use certified non-GMO ingredients.

In recent decades, soy foods have garnered increasing attention for the amount of isoflavones they contain. These phytoestrogens are being extensively studied for their potential health effects ranging from heart disease and breast cancer prevention to bone mineral density reduction in post-menopausal women. Current evidence, however, is far from conclusive, and much remains to be learned about these compounds.⁶

Of additional note, soybeans do contain high levels of phytic acid, a compound sometimes referred to as an “anti-nutrient,” which is not destroyed or reduced during the conventional manufacturing process for soy milk.⁷ Phytic acid has a high affinity for binding minerals such as calcium, iron, magnesium, and zinc and can render these nutrients unavailable for absorption. This effect, however, only occurs when such minerals are ingested simultaneously with phytic acid.

Almond Milk

Almond milk is made from ground almonds and water. It is quickly gaining in popularity, especially among those avoiding soy due to allergies or other health concerns. It is perhaps best known for being low in calories, typically between 30 and 50 per 8 oz. cup (unsweetened), or about one-third the calories of 2% cow’s milk. Sweetened varieties, however, can contain up to 90 calories per cup and 16 g of sugar.

Nut milks in general tend to be highly diluted with water. While this allows them to be relatively lower in calories, this also means that they supply minimal amounts of the nutrients typically found in nuts, including protein, manganese, magnesium, and copper. A major drawback of almond milk is that the protein content from the almonds is strained out of the milk along with the pulp; hence, it contains very little protein – usually only 1 g per 8 oz. cup, compared to 8 g in cow’s milk.

Through fortification, almond milk can offer a comparable amount of vitamins and minerals as cow’s milk – and in some cases, can offer more. However, it is still devoid of most B vitamins, essential fatty acids, and many trace elements such as zinc and copper. One unique aspect of almond milk is its high vitamin E (alpha tocopherol) content, with one cup offering up to 10 mg, or 50% of the daily value for adults.

Rice Milk

There are not many advantages to rice milk over other plant-based milks, but it is likely the most hypoallergenic of all non-dairy alternatives. Though usually derived from boiled brown rice and brown rice starch, it has no fiber and a thin consistency. It has considerably less protein than cow’s milk (only 1 g per 8 oz. cup) and a very small amount of natural calcium, though most brands are calcium-fortified and enriched with vitamins A, D, and B12. It is also low in fat; however, some manufacturers do add vegetable oil as an emulsifier and stabilizer.

Rice milk generally tastes sweeter than cow’s milk, owing to the addition of sweeteners (usually brown rice syrup) and vanilla. It is also significantly higher in carbohydrates.

Oat Milk

Oat milk is made from oat groats (oats that have been cleaned, toasted, and hulled), water, and potentially other grains and beans, such as triticale, barley, brown rice, and soybeans. It has a mild flavor and is slightly sweet. Its consistency is similar to that of 1% or skim milk.

Oat milk is low in overall calories, cholesterol, and saturated fat. It is higher in fiber than other milk alternatives, with 2 g per cup or sometimes more, depending on whether oat bran has been added. It also contains iron, vitamin E, and folic acid. In addition, it offers 4 g of protein per cup, which is relatively higher than most other non-dairy alternatives. At the same time, naturally occurring sugars give this beverage a higher carbohydrate content.

Depending on the manufacturer, oat milk could be another viable option for people with nut and seed allergies. It is important, however, to read the label for added ingredients that could be allergens.

Coconut Milk

Made from grated and squeezed coconut meat, this high-calorie, high-fat beverage is not for drinking straight-up but is usually reserved for cooking, especially in southeast Asian cuisine. It is often found canned and in the ethnic foods section of the grocery store. It has a natural, creamy thickness with a mild nutty flavor.

A 1-cup serving of canned raw coconut milk contains 445 calories and 48 g of fat, of which 43 g are saturated. Recently, however, manufacturers are now offering “coconut milk beverage,” which is essentially coconut milk that has been diluted with water, to appeal to consumers who seek to drink it more regularly. While this type of diluted coconut milk has far fewer calories and much less fat, it also has very little protein – less than 1 g per 8 oz. cup. This version of coconut milk is usually found in cartons (not cans) in the dairy aisle.

Whether concentrated or diluted, coconut milk offers medium-chain triglycerides and a relatively high amount of potassium. If fortified, it can serve as a good source of vitamin D and can also supply up to 50% more calcium than dairy milk. In addition, coconut milk contains fiber and iron, two notable departures from cow’s milk.

Hemp Milk

Though unlikely to ever gain the same kind of popularity as soy or almond milk, hemp milk is considered ideal for people who cannot consume gluten, nuts, and/or soy. It can also be a viable option for those who are on a starch-limited diet and/or must avoid oligosaccharides.

Hemp milk is made from the hulled seeds of the industrial hemp plant, which includes varieties of Cannabis sativa that are low in the psychotropic substance tetrahydrocannabinol (THC) and are grown for food and textile uses. It has an earthier flavor that may be off-putting to some consumers and/or lead them to buy the sweetened versions.

Hemp milk naturally contains more protein than other non-dairy alternatives, but at 2-3 g per 8 oz. cup, it is still not a particularly good source. It does offer a three-to-one ratio of omega-6 to omega-3 essential fatty acids, including around 1,000 mg of alpha-linolenic acid. Other nutrients include magnesium and phytosterols, as well as some calcium, fiber, iron, and potassium.

Pea Milk

Pea milk is one of the newer dairy-free milk alternatives, with only one major manufacturer currently in the U.S. but a second one gearing up to introduce its own line soon. Made from yellow field peas, this beverage is poised to gain more popularity, owing largely to its naturally high protein content (at least 7 g per 8 oz. cup). During manufacturing, yellow peas are milled into flour, which is then processed to separate the protein content from the fiber and starch, and the protein is then further purified and blended together with water and other ingredients. This is a departure from most nut-based milks, in which the protein content is removed and never reintroduced.

Like most other non-dairy alternatives, pea milk is fortified to contain 150% more calcium than cow’s milk. Moreover, its taste and consistency is actually very close to cow’s milk. An added benefit: yellow peas are easy and inexpensive to grow, so pea milk carries a much lower water footprint than almond milk and a much smaller carbon footprint than cow’s milk.⁸

Cashew Milk

With only 60 calories per cup and no saturated fat or cholesterol, unsweetened cashew milk is often considered a good option for those looking for a creamier alternative to almond milk without the fat and calories of canned coconut milk. It is made by blending water-soaked cashews with water.

Like almond milk, after the pulp is strained away, most of the protein content and naturally occurring vitamins and minerals in cashews ends up being lost. Through fortification, however, cashew milk can offer close to 50% more calcium than cow’s milk. Fortified cashew milk can also be an excellent source of vitamin D. In addition, one 8 oz. cup contains 50% of the recommended daily value for vitamin E.

Flax Milk

With a similar nutrition profile to that of almonds, flax milk is low in calories (around 25 kcal in 1 cup of unsweetened) and very little protein. Flax milk is made commercially by combining cold-pressed flax oil with water, thickeners, and emulsifiers. Flax milk has the additional benefit of 1,200 mg of omega-3 fatty acids (alpha-linolenic acid) per 8 oz. cup. It is also fortified with calcium, vitamin D, and vitamin B12, though not to the same degree as some other non-dairy alternatives.

Flax does contain a very high amount of phytoestrogens – over three times that of soy – but it is unclear how much remains in the oil after the seeds are pressed. And again, the potential health effects (both positive and negative) of these compounds are still being extensively researched.

Potato Milk

Potato milk is another newcomer to the non-dairy milk scene. It is not widely available at grocery stores, but it can be ordered online. Commercially, it is usually found in powdered form. Like rice milk, potato milk is high in carbohydrates but low in protein, though it is usually fortified with calcium and vitamins. It is also a good option for those who may have a soy or nut allergy, as well as those following a gluten- and/or casein-free diet, although consumers should read the label to check for potentially allergenic additives.

In addition to providing as much calcium as cow’s milk, potato milk provides more iron than many other non-dairy alternatives.

CONCLUSION

A growing number of consumers are opting for plant-based milk substitutes, either for medical reasons or as a lifestyle choice, and as a result, the current generation of plant-based milks continues to expand. Table 3 outlines the pros and cons of the various types of non-dairy milk alternatives. The nutritional profile of each type of “milk” depends not only on the plant source, but also the manufacturing process and the degree of fortification. These factors are especially important when considering the protein, vitamins, minerals, and sugar in each serving. Most non-dairy milk alternatives are fortified to provide a reasonable amount of calcium and vitamin D, although amounts of other micronutrients are often unknown. Besides taste and texture, protein and added sugars are perhaps the most widely variable attributes among plant-based milks. Consumer awareness, therefore, is important when plant-based substitutes are used to fully replace cow’s milk in the diet.

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A Special Article

Arsenic Levels in Celiac Patients

January 2018 • Volume XLII, Issue 1

Runa Diwadkar Watkins,

Anca Safta,

Dana Hong,

Elaine Lynne Leonard Puppa,

Samra Sarigol Blanchard

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For persons with celiac disease, wheat, barley and rye trigger an autoimmune response in the small intestine, specifically destroying the villi of the duodenum and triggering systemic inflammation. To avoid this immune response, people with celiac disease substitute rice and rice products for wheat, barley and rye. Concerns regarding arsenic levels in rice have prompted the celiac community to question whether increased rice consumption puts them at an increased risk for arsenic toxicity. Some studies have suggested children may be at greater risk than adults. The purpose of this study was to evaluate the risk for increased arsenic levels in persons with celiac disease.

Background:

Methods:

A retrospective chart review of 60 charts was performed for patients seen at a Mid-Atlantic celiac clinic between July 2012 and June 2014. Arsenic levels in biopsy-proven pediatric and adult celiac patients were reviewed. Serum arsenic levels were compared to established normal values; the length of time patients were adherent to a gluten free diet was recorded. Pediatric celiac patients were compared to adult celiac patients.

Results:

Thirty-nine patients had arsenic levels reported. The duration of time between diagnosis to laboratory collection of arsenic levels ranged from four months to 10 years. The mean duration between diagnosis and laboratory collection was 2.35 years for the pediatric group and 3.31 years for the adult group. All patients had normal serum arsenic levels.

Conclusions:

Rice consumption did not increase risk for arsenic toxicity in a retrospective study of serum arsenic levels for patients with biopsy proven celiac disease, irrespective of the duration of gluten free diet.

Runa Diwadkar Watkins, MD¹ Dana Hong, MD¹ Elaine Lynne Leonard Puppa, RN, Med, MSN¹ Anca Safta, MD² Samra Sarigol Blanchard, MD¹ ¹Department of Pediatrics, University of Maryland, Baltimore, MD ²Department of Pediatrics, Wake Forest University, Winston-Salem, NC

INTRODUCTION

Celiac disease is an autoimmune enteropathy triggered by gliadin proteins found in wheat, barley and rye, commonly referred to as glutens. The disease is characterized by increased intestinal permeability, systemic inflammation and damage to the villi of the small intestine resulting in impaired nutrient absorption.¹ The prevalence of celiac disease in the United States is approximately 1:133 individuals.² However, the majority of persons in the United States remain undiagnosed.² Typical symptoms include dyspepsia and diarrhea.^3,4 Atypical cases may present with a variety of symptoms including short stature, fatigue, rash, anemia, folate deficiency, osteoporosis, arthralgias and myalgias, migraine, peripheral neuropathy and seizure disorder.⁴ The only treatment for celiac disease is strict elimination of any exposure to the gliadin proteins, as gluten consumption as low as 20 ppm (1/4 tsp flour) may trigger the autoimmune response.⁵

Wheat, barley and rye constitute the staple grains of the United States. Although quinoa, amaranth, corn and other grains that do not contain gluten have recently come into the market, rice remains the staple grain of the celiac diet in most parts of the world. A 2012 Consumer Report article detailed concerns over arsenic levels in food in general, and rice in particular.⁶ In addition, the Food and Drug Administration (FDA) began its own investigation into the levels of arsenic in rice in 2012.⁷ Concerns over the quality of rice and results of accumulated consumption over time began to emerge from the celiac community.^8-12 A 2014 study estimated that rice-based foods contained potentially dangerous levels of arsenic with consumption of 0.45-0.46 µg per kg bodyweight.¹³ Patients in our practice began to express concerns for the level of arsenic they were consuming, not just as rice itself, but also in their baked goods and other gluten free foods that contained rice flour and rice starch as a primary ingredient.

Arsenic is a metallic trace element widely distributed in the environment as a result of natural and human activity.¹⁴ Its organic forms are believed to be essential to many forms of mammalian life.¹⁵ The human body rapidly eliminates organic arsenic compounds such as those found in seafood.¹⁶ However, the inorganic forms of arsenic are more problematic. The World Health Organization (WHO) categorizes inorganic arsenic as a class I human carcinogen.^17,18 Long-term exposure can lead to arsenicosis, a condition of arsenic toxicity due to chronic exposure. Arsenicosis can manifest itself in diseases involving the skin, cardiovascular, nervous, hepatic, hematologic, endocrine or renal systems.

Arsenic compounds occur in soils, and contamination can be widespread in the environment. Volcanoes disperse arsenic containing ash. Metal smelting, burning fossil fuels, pesticide production and use, and drilling of water wells may also mobilize arsenic in the soil.^6-7,19 Ground water dissolves the mineral from the soil creating a variety of salts across a wide range of conditions.²⁰

For most people, diet is the largest source of exposure to arsenic with mean dietary intakes of total arsenic of 50 -60 mcg/day. Intake of inorganic arsenic ranges from 1-20 mcg/day when rice and/ or infant rice cereal are included in the diet. Rice contains the highest level of inorganic arsenic and arsenic concentrations ranging from 0.05 to 0.4 mcg/g of rice.⁷

Arsenic accumulation in the rice plant increases markedly under flooded conditions due to the soluble nature of arsenic salts. Arsenic levels vary throughout the world with highest arsenic contamination found in ground water affecting Bangladesh, India, Vietnam, Thailand, and Nepal. Contamination of water is largely due to heavy industry contaminants. Within the United States, rice grown in the south-central US contains higher average total arsenic concentrations compared to California.¹⁵ Brown rice contains higher levels of arsenic because the arsenic tends to concentrate in the area near the surface of the grain, the area polished off to create white rice. ²¹

Children have dietary arsenic exposure from 2 to 3 times greater than that of adults and may be the most vulnerable.²² Considering rice and rice based foods contain high levels of inorganic arsenic, pediatric celiac patients may be a particularly high-risk category.²³ In these patients, rice and rice based foods are the main edible substitutes of gluten based products.

The American Academy of Pediatrics (AAP) in November 2014 advised pediatric patients to reduce exposure to arsenic in rice, in response to FDA advisory group which conducted a risk assessment regarding acceptable levels of arsenic in drinking water and diets.²⁴ The AAP recommended interim advice was directed, in particular, toward infant rice cereal, which is used as a thickening agent in feedings for infants and older children, and as a bland introductory food during weaning. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) in 2015 published a consensus statement that rice contains high levels of inorganic arsenic and its intake during childhood is likely to affect long- term health. The recommendation was to limit the intake of inorganic arsenic as long as possible and reduce intake of inorganic arsenic exposure from food by including a variety of grains such as oat, barley, wheat and maize in the diet.

Chronic and continued exposure to arsenic achieves steady-state concentrations in blood and urine as well as arsenic accumulating in hair and nails.²⁵ Urinary arsenic reflects arsenic excretion but may not reflect tissue burden. Blood arsenic levels better demonstrate both recent exogenous exposure and an individual’s total internal arsenic burden.²⁵

METHODS

A retrospective chart review of celiac clinic patients with arsenic orders placed between July 2012 and June 2014 was conducted. Physicians obtained routine nutritional and serologic markers to monitor the nutritional status and antibody levels of their patients diagnosed with celiac disease. Blood arsenic levels were ordered in conjunction with annual nutritional and serology follow up in established celiac patients or within six months for newly diagnosed celiac patients as part of routine care.

Blood arsenic level was selected as a marker to limit the number of extra procedures. The value of evaluating blood or urine arsenic has been shown to be equivocal in detecting chronic exposure and body’s burden of the toxin.^25-26 Chronic and continued exposure to arsenic achieved steady state concentrations in blood and urine. However, urine arsenic levels reflect arsenic excretion and not actual tissue burden.¹⁴ The blood arsenic levels may be a better indicator of recent exogenous exposure and tissue burden.

The review identified sixty unique patients on a gluten free diet from the University of Maryland Medical Center Division of Pediatric Gastroenterology and Nutrition. Inclusion criteria included an order for blood arsenic levels and a diagnosis of celiac disease with confirmatory small bowel biopsy. Demographics, diagnoses, method of diagnosis, date of diagnosis and lab values for arsenic level were reviewed for each patient. Four patients were excluded for lack of follow up visit and 15 patients were excluded as the laboratory studies were ordered but not resulted in the patient chart. Of the remaining 41 patients, the diagnosis of celiac disease was made by biopsy of small bowel on esophagogastroduodenoscopy (EGD) for 39 patients as recommended by NASPGHAN. The arsenic levels from lab panels of the 39 patients who met inclusion criteria were reviewed.

RESULTS
Demographics

Thirty-nine patients, ages ranging from 5 to 68 years of age, met the inclusion criteria for review. The mean age for the group was 20 years of age with a bimodal distribution. Twenty-two patients were pediatric patients, defined as less than 18 years of age. The median age of reviewed patients was 10 years old for the pediatric group and 30 years old for the adult group.

RESULTS

The span for duration of time from diagnostic biopsy to blood arsenic collection ranged from 4 months to 10 years. The mean duration period from diagnosis to collection of arsenic levels was 2.35 years for the pediatric group and 3.31 years for the adult group. All patients had normal serum arsenic levels (Table 1). Seven patients had rice exposure of greater than 6 years and the arsenic levels did not differ from the other patients with shorter exposure. This pilot study found no abnormal levels of serum arsenic in patients diagnosed with Celiac Disease, eating a gluten-free diet. Longer exposure to a rice containing diet, determined by an earlier age of diagnosis of Celiac Disease, demonstrated no increased risk of arsenic accumulation for either pediatric or adult celiac patients.

DISCUSSION

Although significant speculation regarding the potential risk of high arsenic exposure in persons can be found in the literature regarding persons with celiac disease due to their higher rice consumption on a gluten free diet, no published literature is available to substantiate the risk. Bioavailability of arsenic from rice can be very high due to the ability of rice to sequester arsenic absorbed from soil and water.^24-26 Existing arsenic levels in rice are often exacerbated by contaminated cooking water.^20,27 The American Academy of Pediatrics, FDA and NASPGHAN committee on nutrition recommends limiting the intake of rice in diet and to introduce variety of grains including oats, wheat and barley in vulnerable populations.^7,24,26,28 This limitation of rice intake by introducing variety of grains is not possible for celiac patients who have restricted diets where oats are limited and wheat, barley, or rye and oats are eliminated.⁴

This pilot study suggests that celiac patients who are on an exclusive gluten free diet may not need to have arsenic levels checked along with their other follow up laboratory studies. We did not see any abnormal serum arsenic values for celiac patients who were on exclusive gluten free diets for a longer duration of time. This study highlights the need for clinicians to be aware of the concerns that parents of celiac patients may be facing in the dietary restrictions but no further work up is recommended based on this limited set of data from the pilot study.

This study should be interpreted within the context of its limitations. First, because of the retrospective design, we could not perform blood arsenic levels at time of diagnosis and later after therapy with a gluten free diet for comparison. Second, the gluten free diet of each celiac patient did not account for varied intake in amount of rice consumption for each patient or the origin of the rice. Variations existed in the definition of normal range of arsenic levels between lab facilities that were used to define cut off values. Standardization of laboratory collection at the same resulting facilities would eliminate this variability in comparison of values. Lastly, the power of the study can be improved if an increased number of subjects were included. Future studies should focus on improving the shortcomings as highlighted above. Newer concerns have also suggested arsenic levels possibly being higher in urine samples in those with a strictly gluten free diet. This value was not tested in our study, but would need to be considered in future studies as well.

Most studies of arsenic levels are laboratory based and do not allow for the complex interaction of systems involved in human digestion. Several other modifying effects from the environment influence the human body’s ability to detoxify arsenic that may have influenced the results of this study. Folate and folic acid supplements have demonstrated the ability to lower blood arsenic levels in persons exposed to high levels of arsenic in the drinking water.²⁹ Arsenic, therefore, presents a greater threat to persons who are folate deficient. Likewise, antioxidants from brassicas and other vegetables have also shown protective effects in vitro and been hypothesized to provide a protective effect in the human diet.¹⁶ The soil microbiome is known to degrade inorganic arsenic and the human microbiome has demonstrated a similar effect in vitro.^16,30 Based on these findings and interpretations, it is not useful to obtain nor follow serum arsenic levels in those with Celiac Disease.

CONCLUSION

In conclusion, the serum arsenic levels were found to be normal in our patients with Celiac Disease. Adherence to a strict gluten free diet did not pose a risk of elevated serum arsenic levels. It is suggested that elevated serum levels of arsenic is correlated with acute toxicity, which did not occur in our cohort. We strongly recommend that patients with Celiac Disease do use high quality rice products and future studies may point to checking urine arsenic levels after being on a strict gluten free diet for a long period of time.

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NUTRITION ISSUES IN GASTROENTEROLOGY, SERIS #183

Part I Enteral Feeding Barriers: Pesky Bowel Sounds & Gastric Residual Volumes

January 2019 • Volume XLIII, Issue 1

Carol Rees Parrish,

Stacey McCray

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Enteral nutrition (EN) is an effective way to nourish patients; however, many barriers prevent consistent and effective delivery of EN in the hospitalized patient. Clinicians must focus on interventions that will make our patients comfortable while their EN is infusing. Part I of this four part series critically evaluates two of the most common barriers to EN: the use of bowel sounds to assess readiness for EN and gastric residual volumes to assess tolerance of EN. Strategies to manage such obstacles in the clinical setting will be provided.

Upcoming in the series:

Part II Enteral Feeding: Eradicate Barriers with Root Cause Analysis and Focused Intervention
Part III Jejunal Feeding: The Tail is Wagging the Dog(ma): Dispelling Myths with Physiology, Evidence, and Clinical Experience
Part IV Enteral Feeding: Hydrating the Enterally-Fed Patient—It Isn’t Rocket Science.

Carol Rees Parrish MS, RDN Nutrition Support Specialist, Digestive Health Center, University of Virginia Health System, Stacey McCray RDN Coordinator, Nutrition Support Training Programs, University of Virginia Health System, Digestive Health Center, Charlottesville, VA

INTRODUCTION

Enteral feeding is an effective way to nourish those patients unable to meet nutritional needs by mouth alone. However, many barriers exist in the hospital setting that interfere with the delivery of the prescribed EN (Table 1). Confirming our clinical experience, many studies have demonstrated that patients routinely receive only 45-65% of EN ordered,^1-5 and only 84% was achieved in a recent study that set out to ensure a targeted level of EN was delivered.⁵ To overcome this track record, we must carefully examine each aspect of EN delivery for potential barriers to adequate nutrition support. Many current practices surrounding the provision of EN are not evidenced-based, nor physiologically sound. One of the most common reasons for EN to be held is “gastrointestinal (GI) intolerance.” Many reports of ‘GI intolerance” are based on unproven monitoring techniques and years of past assumptions about how the GI tract works. While it is true that hospitalized patients can have significant GI issues, little evidence exists to support many of the practices used to “monitor” tolerance to EN. Developing a successful EN regimen requires the following:

Full understanding of normal GI anatomy and physiology
Knowledge of current evidence behind the practice of enteral nutrition
Clinical experience as a bedside practitioner

The goal of this four part series is to review basic GI anatomy and physiology, discuss how this relates to EN, identify common barriers to EN, and identify strategies to overcome these obstacles. With a better understanding of the GI tract and normal GI function, the clinician will be better equipped to address the root cause of EN delivery barriers and intervene appropriately to improve provision of EN. Part I critically evaluates two of the most common barriers to EN: the use of bowel sounds to assess readiness for EN and gastric residual volumes to assess tolerance of EN.

BOWEL SOUNDS

Auscultation of bowel sounds (BS) has historically been used to assess bowel function and readiness for oral diet or EN. Despite widespread use, the practice of auscultating BS has never been validated as a marker of GI function; hence its clinical value remains largely unstudied and subjective. In fact, no evidence exists supporting the correlation between bowel sounds and peristalsis, or the need to wait for BS prior to EN initiation.⁶ To the contrary, two studies have demonstrated that there is a great deal of inter-rater variability among physicians when listening to BS, and that auscultation of BS are unreliable as an indicator of peristalsis and GI function.^7-8

Enhanced Recovery after Surgery (ERAS) protocols are multimodal peri-operative protocols aimed at enhancing organ function and decreasing surgical complications resulting in earlier hospital discharge. Most ERAS protocols include early initiation of an oral diet (often post-op day 1). Assessment of BS is not included in any ERAS protocols. This is in contrast to conventional care protocols that hold oral and EN until ‘bowel function returns’—most often assessed by BS or passage of gas. The recent implementation and advancement of ERAS protocols demonstrate that early oral or EN is not only possible, but beneficial to patients. ERAS protocols have demonstrated.^9-11

Earlier return of bowel function & decreased incidence of post-op ileus
Less nausea (through prophylactic nausea medication)
Decreased complication rates and shorter hospital length of stay
Earlier resumption of normal activities
Increased patient satisfaction
Significant cost savings

In summary, experience from ERAS protocols suggests that there is no benefit to using BS as an indicator of GI function and it should be removed as a potential barrier to nutrition supports goals.

ASSESSMENT OF GASTRIC RESIDUAL VOLUMES

Gastric residual volumes (GRV) for decades have been used to ‘measure’ tolerance of EN. A recent nursing survey of 582 nurses in 5 major hospitals found that 89% of nurses would terminate EN for GRVs > 300mL.¹² However, this practice is counterintuitive to normal gastric anatomy and physiology. The stomach is a reservoir and the idea that having some gastric residual is abnormal or a problem contradicts its physiologic role.

It is important to bear in mind that a GRV in an enterally-fed patient is not only comprised of EN (i.e. what goes in is not the only thing that comes out). The volume of endogenous secretions (salivary and gastric secretions) that pass through the stomach daily is approximately 2-4 liters (Table 2). Remember, when any volume is put into the stomach, the stomach responds by adding its own gastric juices as part of its physiologic role.^13,14Borgstrom demonstrated a 3-5 fold dilution of a test meal from stomach into duodenum over a 4 hour period—500mL/625kcal test meal diluted to a volume of 1500-2500mL.¹⁵The total daily volume of endogenous secretions, oral intake, EN, medications, and water flushes can be > 6 liters per day (∼ 230mL/hr) above the pylorus alone. With this volume in mind, one might argue that standard GRV thresholds (60-150mL) are less than endogenous secretions, and therefore, by definition, emptying must be occurring. When evaluating the significance of GRV, all the components contributing to that volume should be considered.

In addition to the physiologic aspects of GRVs, there are practical and institutional limitations, as well. No standard definition of a GRV exists because the volume that constitutes a significant GRV has never been prospectively studied in a randomized fashion. EN is often held based on an arbitrary number chosen by the hospital or found in textbooks. There is little agreement on how frequently GRV should be checked and whether the GRV should be returned to the stomach (and, if so, how much should be returned?).¹⁶ The location of the tip of the feeding tube in the stomach will also affect the amount of GRV. For example, a PEG tube placed high in the stomach may not produce a significant residual because it sits above the air-fluid level of dependent gastric contents. Conversely, a nasogastric tube may produce more GRV simply due to its position in the stomach (see section on pooling effect below).

Gastric Emptying and the Pooling Effect

Normal gastric emptying is quite swift. Liquid emptying is preserved even in severe gastroparesis.¹⁷ However, liquids empty from the stomach by receptive relaxation and gravity; therefore, the supine positioning of many hospitalized patients is not optimal for gastric emptying. In the supine position, the anatomy of the stomach is such that the fundus is in the most posterior/superior/left portion and the antrum is in the anterior/inferior/right portion. When the patient is supine or semi-recumbent, liquids can collect in the fundus because it is posterior. Hence, when a patient is supine or at low backrest elevation, the stomach “drapes” over the spine, and with the addition of gravity, gastric secretions may pool in the most dependent portion. When the patient turns to the right side down position, liquids move past the spine to the more anterior antrum and thus can pass into the duodenum. In the upright position, the fundus empties into the more dependent body and antrum and into the duodenum. Therefore, the stomach generally empties best when the patient is on the right side when lying flat or semi-recumbent, or when the patient is fully upright. For radiology photo images illustrating this concept, see also the 2008 article in the Practical Gastroenterology series on GRVs.¹⁸

Most nasogastric feeding tubes fall into the most dependent part of the stomach, the fundus, which is not contractile and furthest from the pylorus. Aspirating a GRV from the fundus may retrieve a much greater volume than from the antrum. Although anecdotal, one intervention that is used at UVAHS should a patient’s residual be checked and be elevated beyond what the team is comfortable with, is to put the patient on their right side (while semi-recumbent) for 15-20 minutes, after which the residual is rechecked. Taking advantage of gravity by turning patients on their right side where the pylorus is located (while maintaining backrest elevation at 30 degrees or greater), may enhance liquid emptying from the stomach, and decrease the amount of GRV detected. For more information on this topic, ask your radiologist about how they perform a barium swallow (not to be confused with a modified barium swallow).

Back to GRVs

Monitoring of gastric residuals is often thought to reduce the risk of aspiration and pneumonia in higher risk, critically ill patients. However, several studies have shown that increasing the threshold for gastric residuals (up to 400-500mL) did not increase the incidence of pneumonia.^19,20 Several studies have also shown that raising the level of GRV and decreasing the frequency (or eliminating checks altogether) results in more EN received^21,22 without significantly increasing the incidence of ventilator associated pneumonia. The use of GRVs to prevent aspiration pneumonia suggests that only those patients who are enterally fed are at risk for aspiration. Do we check GRVs in patients on oral diets during the day, but supplemental EN overnight? What about patients receiving parenteral nutrition (PN) or IV fluids (often our sickest patients)? Some studies have shown that patients receiving PN have a higher rate of pneumonia than those enterally-fed.^23,24

Despite the lack of evidence to support monitoring GRVs, a great deal of nursing time is spent on this task, and patients miss a significant amount of EN for what may be a clinically unimportant (and arbitrary) reason. At least one study has also shown that frequent GRV checks may lead to more frequent clogging of feeding tubes.²⁵ Williams, et al. also concluded that reducing the frequency of residual checks saves nursing time, decreases risk of contamination of feeding circuit, and minimizes risk of body fluid exposure.²⁶ Ultimately, not checking GRV allows the nurse more time with their patients to focus on steps that have been shown to decrease aspiration pneumonia (good oral hygiene, backrest elevation, etc.), while allowing patients to meet important nutrition goals.

Time To Move On?

In 2016, the American Society for Enteral and Parenteral Nutrition (ASPEN) and the Society for Critical Care Medicine (SCCM) jointly came out with practice guidelines questioning the practice of checking GRVs. Their conclusions can be summarized as follows:²⁷

GRVs should not be used as part of routine care to monitor ICU patients receiving EN.
For those ICUs where GRVs are still utilized, holding EN for GRVs < 500mL in the absence of other signs of GI intolerance* should be avoided. *GI intolerance is defined as:
“Vomiting, abdominal distention, complaints of discomfort, high NG output, high GRV, diarrhea, reduced passage of flatus and stool, or abnormal abdominal radiographs.”

While GRVs are not an effective way to monitor tolerance to EN, it is still extremely important to monitor hospitalized patients for signs and symptoms of impaired gastric emptying which is common in the hospital setting. Clinicians should be aware of circumstances that put patients at risk for gastroparesis or altered GI function and develop an individualized plan accordingly. It is crucial to pay attention to abdominal symptoms such as distention, complaints of fullness, tenseness, guarding, firmness, bloating, pain, nausea or vomiting. Patients should also be monitored for constipation, especially in those on narcotics. If your institution does continue to check GRVs, see Table 3 for suggestions to intervene. Finally, see Appendix I for one institution’s justification to phase out routine GRV checks.

Additional Considerations Physiologic Response to Enteral Feeding Initiation and the Ileal Brake

An initial increase in GRV has been documented the first few hours of EN initiation, but this effect subsides rather quickly.²⁸ Kleibeuker provided 15 healthy volunteers with 200mL/hr of EN for 450 minutes (7.5 hours).²⁸ GRVs were checked every 30 minutes beginning at 120 minutes of EN infusion. The author found the highest GRVs occurred at 120 minutes, then decreased with continued infusion.

The ileal brake is a feedback mechanism within the ileum that regulates the passage of food through the gut.²⁹ When the distal intestine identifies nutrients that seem to have escaped absorption higher up in the small bowel, a signal is sent to slow peristalsis (including gastric emptying).^30,31 Therefore, it is not uncommon for patients to have an increase in nausea or other GI symptoms upon initiation of jejunal feedings if nutrients escape to the ileum.

In either circumstance above, if patients experience increased GRVs or an increase in nausea upon initiation of feeding, a brief decrease in rate with a slower advancement may help this transition. Use of a scheduled antiemetic for a few days can help also. However, patients should be able to quickly advance to goal flow as these mechanisms subside.

A Word About Backrest Elevation

While there is little evidence to support GRV checks, there is clear evidence available to support a decreased aspiration risk when backrest elevation (BRE) is maintained.^32-39BRE of < 30 degrees is one of the most modifiable risk factors consistently and strongly associated with aspiration, especially in bedbound patients with altered sensorium or impaired swallow. This seemingly simple (but underutilized) intervention is not easy to accomplish. Two studies reported that critical care nurses consistently over-estimated the BRE level.^37,40 Another study found that nurses self-reporting of BRE were consistent with observed levels of 28 degrees for intubated patients.⁴¹ In all of these studies, actual BRE fell far short of the recommended 45 degrees regardless of the nurses’ perceptions. A summary of studies evaluating BRE in hospitalized patients can be found in Table 4.

There are a number of things that clinicians can do to help ensure that backrest elevation is maintained. First, educate all members of the team that they share this responsibility—it really does take a village. Education should not be a one-time event, but should be ongoing at regular intervals (e.g. quarterly). Note that it is not necessarily accurate to use the head of bed gauge since the gauge measures the level of the head of bed and does not measure the patient’s level of BRE. For those who slide down in the bed, a technique might include elevation of the HOB to approximately 20-30 degrees, then changing the angle of the whole bed to assure BRE (i.e., reverse trendelenberg). Physician orders for backrest elevation may help with compliance. If not already a part of routine order sets, any member of the healthcare team can request such an order from the physician or nurse practitioner. Finally, regular monitoring of institutional practices is necessary, as adherence with guidelines fluctuates over time.

SUMMARY

EN is an effective way to nourish patients unable to meet their nutritional needs, particularly in the acute inpatient setting. However, for EN to be effective, patients need to receive the goal (“dose”) intended. Many barriers exist in the hospital setting that thwart patients from meeting key nutrition goals, without good evidence to support holding EN for these issues. Instead of perpetuating the myth that EN causes complications, clinicians must focus on the underlying conditions and interventions that will make our patients comfortable while their EN is infusing. This article specifically addresses bowel sounds, gastric residual volumes and backrest elevation, and provides the reader with an opportunity to reevaluate how one approaches these barriers in order to maximize nutrient delivery in the enterally-fed patient.

Download Tables, Images & References

INTRODUCTION

Malnutrition Coding: Beyond the Money

Malnutrition Treatment: It Takes a Healthcare Village

Documentation Guidance for RDNs and LIPs

Building the Foundation: Success Story of Documentation

CONCLUSION/CALL TO ACTION

INTRODUCTION

Etiology and Nomenclature

Gastroparesis and Chronic Nausea and Vomiting Syndrome

Dietary Symptom Management

Nutritional Support

Other Causes of Chronic Nausea and Vomiting Functional Dyspepsia

Cyclic Vomiting Syndrome (CVS) and Abdominal Migraine

Rumination Syndrome

CONCLUSION

CASE HISTORY

Discussion

INTRODUCTION

Physiology

Pathophysiology

Clinical Manifestations

Diagnosis

Elevated B12

Methylmalonic Acid and Homocysteine

Determining Etiology

Screening

Management

CONCLUSION

INTRODUCTION

SIBO and IBS: Are They Related?

Dysbiosis and Constipation

Testing: How to Come to the Diagnosis

Medical Therapies: Understanding Current Treatment Options Non-Pharmacologic Treatment Strategies

Pharmacologic Treatment Strategies

SUMMARY

INTRODUCTION

Dietary Intervention for IBS – The Low FODMAP Diet

Lactose

Fructose

Polyols

FODMAP Diet Implementation

FODMAP Diet Phases

Phase 1. Restriction

Maintenance Phase

Additional Considerations

CONCLUSION

INTRODUCTION AND EOSINOPHILIC ESOPHAGITIS OVERVIEW

CONCLUSIONS

The Rise of Plant-Based Milks

How Do Plant-Based Milks Compare to Cow’s Milk?

Soy Milk

Almond Milk

Rice Milk

Oat Milk

Coconut Milk

Hemp Milk

Pea Milk

Cashew Milk

Flax Milk

Potato Milk

CONCLUSION

Background:

Methods:

Results:

Conclusions:

INTRODUCTION

METHODS

RESULTS Demographics

RESULTS

DISCUSSION

CONCLUSION

INTRODUCTION

BOWEL SOUNDS

ASSESSMENT OF GASTRIC RESIDUAL VOLUMES

Gastric Emptying and the Pooling Effect

Back to GRVs

Time To Move On?

Additional Considerations Physiologic Response to Enteral Feeding Initiation and the Ileal Brake

A Word About Backrest Elevation

SUMMARY

Other Causes of Chronic Nausea and Vomiting
Functional Dyspepsia

Medical Therapies: Understanding Current Treatment Options
Non-Pharmacologic Treatment Strategies

RESULTS
Demographics