Page 47 – Practical Gastro

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

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.

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NUTRITION ISSUES IN GASTROENTEROLOGY, SERIS #184

Part II Enteral Feeding: Eradicate Barriers with Root Cause Analysis and Focused Intervention

February 2019 • Volume XLIII, Issue 2

Carol Rees Parrish,

Stacey McCray

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Identifying issues that interfere with adequate provision of enteral nutrition (EN) and getting to the root cause of EN intolerance or complications increases the likelihood that patients will receive the nutrition intended. Part I of this series discussed the practice of listening to bowel sounds and checking gastric residual volumes as determinants of GI tract function. In Part II, several other barriers to effective EN are discussed, including diarrhea, nausea, vomiting, pain, constipation and initiation and progression of EN.

CASE

A 40 year old male was admitted with severe odynophagia, dysphagia & “tube feeding intolerance.” His recent medical history includes squamous cell carcinoma of the tongue. He is now undergoing chemo and radiation therapy, with a percutaneous endoscopic gastrostomy (PEG) placed prior to starting this therapy. His medical history also includes hypertension, alcohol misuse, and significant smoking. His home EN regimen prior to admission was 6 cans per day of a 1.5cal/ mL product, but the patient has only been able to take in 3-4 cans per day. He recently saw an LIP for his inability to tolerate EN and was changed to 2.0cal/ mL product; however, he was admitted right after it was delivered to his home and he had yet to try it. Upon interviewing the patient, it was evident he was in agony and that it clearly hurt him to answer basic questions-swallowing even his own saliva felt like “swallowing ground glass.” Due to the patient’s obvious pain, the interview was kept short and consisted of only yes and no questions. The barriers keeping him from consistently taking his EN were: poor pain control and feeling full/nauseated soon after taking his EN. He stated he took his tube feeding over the course of 30 minutes at home — (i.e., was not bolusing the formula in over 5 minutes), and was also not constipated, despite the use of opiates. The primary team was planning on escalating his pain medications. The nutrition support clinician reviewed the patient’s medication orders and noted an antiemetic ordered “pro re nada (PRN),” but only one dose had been given to the patient in 3 days. It was recommended to the primary team to schedule patient’s antiemetic to every 8 hours vs. prn. Twenty-four hours later, after he had received 3 doses of his antiemetic, the patient was tolerating all of his feedings without complaint.

INTRODUCTION

In this era of high tech medicine, clinical skills may be eclipsed by new technologies, diagnostics, and therapeutic advances. However, basic clinical assessment skills are critical for accurate assessment of the enterally-fed patient. Many issues interfere with patients receiving the full amount of enteral nutrition (EN) ordered (see also Part 1 of this series). Not the least of these issues are patient specific barriers, which are often widely referred to as, “EN intolerance or complications” (Table 1). However, “EN intolerance or complications” is extremely vague and requires further exploration by the clinician in order to effectively intervene. The real problem may be related to the underlying disease state, inadequate or inappropriate medication treatment (such as PRN orders that are never given), or perhaps the wrong medication for the “job.” In some cases, the patient may not be able to articulate what is wrong, and it is easy to attribute the patient’s symptoms to EN. Simply blaming symptoms on EN may prevent the clinician from identifying the root cause of the barrier, resulting in decreased EN delivery to patients. Part I of this 4 part series reviewed the evidence (or lack thereof) behind the use of bowel sounds as a determinant of GI function and the waning (but persistent) use of gastric residual volumes as a surrogate measurement of EN tolerance. Part II will cover other common GI issues that get in the way of effective EN delivery, including diarrhea, nausea, vomiting, pain, constipation, and initiation and progression of EN. With a better understanding of the GI tract and normal GI function, it is possible to overcome many GI barriers and develop successful EN regimens that actually meet the nutritional needs of our patients.

PATIENT’S SYMPTOMS AS A BARRIER

Diarrhea

Diarrhea is an alteration of the normal balance of absorption to secretion within the bowel. Under normal circumstances, nine to ten liters of endogenous and exogenous fluid are introduced to the GI tract each day (see Part I of this series). Yet, the normal stool volume in adults is only 100-200mL. Diarrhea results from increased water content of stool due to an imbalance in intestinal processes involved in the absorption of ions, organic substrates, and thus water. In osmotic diarrhea, stool output is proportional to the intake of the non-absorbable substrate; stool volume decreases quickly with discontinuation of the offending nutrient/agent. In secretory diarrhea, the epithelial cells’ ion transport processes reverse into an active secretory state. The volume of stool output and fluid loss can be very high; however, nutrient absorption often remains intact.

The reported incidence of diarrhea in the hospitalized patient varies greatly from 20% – 70%. This is due to the multiple definitions of diarrhea in the literature, no defined volume or frequency that quantifies diarrhea, subjective diagnoses of diarrhea by both clinicians and patients, and other factors. Lebak identified 33 definitions in the literature, and the definition appeared to be based on the preference of the investigator.¹ It is also of utmost importance to ask patients what their normal stool habits are at home/or pre-illness, so clinicians are not trying to fix something that has been going on long before EN was initiated (although in some cases the problem may still need to be fixed, it is just clearly not the result of EN).

Diarrhea can be both a sign and/or a symptom of an underlying issue, but it is not a disease unto itself. Diarrhea occurs for a variety of reasons in hospitalized patients,2-8 regardless of whether they are on an oral diet, EN, PN or even NPO.^{2,9- 11} (Table 2). In the enterally-fed population, diarrhea has long been associated with (and blamed on) the enteral formula and/or delivery method. However, randomized, prospective trials demonstrating EN as a cause of diarrhea, have yet to be done and diarrhea has yet to be causally linked to EN (liquid in ≠ liquid out).^12-15 As far back as 1981, Bloom remarked, “gastrointestinal upset in nasogastrically-fed patients is not always the result of the tube feeding and should not be an accepted consequence”.¹⁶ The authors went on to carefully explore diarrhea in EN-fed patients and were able to identify medications as the primary causative agents. In fact, in one study of EN-associated “GI intolerance”, diarrhea was observed in 26% (36/137) of patients, while 29% (40/137) exhibited constipation.¹⁷ What is perplexing is that if a patient has diarrhea while on a clear, full, or regular diet, the diet is not typically blamed; hence, why is EN blamed for diarrhea? This assertion is counterintuitive to GI physiology.

Malabsorption

Some clinicians have the misconception that diarrhea equals malabsorption. In fact, the GI tract is so effective in its digestive and absorptive role, >90% of nutrients are completely absorbed within the first 5 feet (150cm) of jejunum in normal subjects.^18,19 A large portion of the GI tract or digestive organ function must be lost to result in malabsorption. Patients with moderately impaired GI tracts are still able to absorb many intact nutrients,^20,21 and even those with a total pancreatectomy are able to utilize greater than 60% of intact protein.²² Patients fed into the duodenum or jejunum do not routinely require a pre-digested formula, as the digestive capacity of the small bowel is enormous. While malabsorption is certainly on the list of things to consider in those patients who have risk factors, only a small percentage of the EN-fed population malabsorb. In any patient suspected of malabsorbing their EN, a 48-72 hour fecal fat collection (done while the patient actually receives the prescribed formula that they are thought to be malabsorbing) will provide the answer.

Contributions of Medications

Medications are a common, but often unrecognized, cause of diarrhea in the EN-fed patient. Liquid medications frequently contain sorbitol or other sugar alcohols, which can be very diarrheagenic.^4,5,10,23,24 Sorbitol is a poorly absorbed polyalcohol; 20-50g/day has been shown to cause osmotic diarrhea, although even 5-10g is enough in some patients.²⁵ For example, one dose of acetaminophen liquid contains 5.47.g of sorbitol/500mg dose; amantadine, 6.4g/100mg; and finally, metoclopramide liquid, 3.5g/10mg (therefore, the diarrheagenic effects of liquid Reglan are NOT from its prokinetic effects as it only is effective on the upper gut, not the colon).²⁶ Liquid medications are also additive in their effect; the more liquid meds, the higher likelihood diarrhea will follow. Diarrhea is often associated with EN in these cases as once enteral access is obtained, medications are frequently changed to liquid form for ease of administration via the feeding tube. Hence diarrhea seems to start at the same time as the EN (Table 2).

Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea and Clostridium difficile (C. difficile) are frequent causes of diarrhea in the hospitalized patient.^{4,6,12,15,27,28} Patients receiving EN are at a higher risk for acquiring C. difficile.⁸ One study reported EN-fed patients were nine times more likely to develop C. difficile-associated diarrhea than matched non-EN-fed patients (possibly from the hands of health care providers); the risk was even greater when patients were fed postpylorically (delivery below the gastric acid barrier may facilitate the introduction and survival of C. difficile organisms).⁸

Hypoalbuminemia

Although hypoalbuminemia has been cited as a risk factor for EN related diarrhea, no evidence exists to support this notion.⁶ Hypoalbuminemia is also associated with sicker patients (ICU, abdominal abscess, etc.), and sicker patients get more infections (hence, more antibiotics), and are in the hospital longer (with even more medications and more infections). These factors are known to precipitate diarrhea. There is no data that patients with hypoalbuminemia absorb less than healthy controls or absorb inadequate amounts.²⁹

Osmolality or Hypertonicity

Despite the perception that osmolality (or hypertonicity) is responsible for triggering diarrhea in patients receiving EN, there is no evidence to support this. The GI tract is adept at diluting and digesting food and liquids of various tonicities. When volume is delivered into the stomach, the volume receptors in the stomach respond by adding a secretory volume.³⁰ After mixing with gastric secretions and saliva in the stomach, chyme leaves the stomach and is further diluted by bile salts, pancreatic enzymes, bicarbonate, and water secreted into the small bowel. Borgstrom demonstrated that a 500mL test meal (625kcal w/ 40% fat, 15% protein, 45% carbohydrate) is diluted to a volume of 1500-2000mL during passage through the duodenum.¹⁸ This process increases the pH and dilutes the solution — “auto-isotonicity” if you will. This is a normal function of the stomach and small bowel. It is incorrect to think that when EN is infused it is the only thing present in the stomach and bowel. One study showed that hypertonic formulas (544mOsm) infused gastrically are nearly isotonic by the time they reach the ligament of treitz (10 inches [25cm] distal from the pylorus),³¹ while another found that hypertonic formulas infused at the ligament of treitz are nearly isotonic 14 inches (35cm) distal in the jejunum.19 Pesola demonstrated a difference in stooling frequency prior to initiation of EN in 39 subjects (5 volunteers, 10 head and neck cancer patients, and 24 ICU patients).³²However, after initiation of full strength, hypertonic EN (Ensure Plus ® – 690mOsm) at 30cal/kg/day by gravity drip or bolus (head and neck patients), no significant difference in diarrhea between groups was found during feeding.³² Jones et al found no evidence to implicate hypertonicity of EN as an etiology of diarrhea in their study.¹⁵ Finally, Kandil et al continuously infused an average of 275mL/hour (range: 198 to 340mL/hour or 5000 to 8650 kcal/day) of standard, polymeric EN into the duodenum of five healthy volunteers before precipitating diarrhea in their subjects.³³ The authors suspected it was the sheer amount of magnesium that was infused with that volume of EN that precipitated the diarrhea (given how poorly absorbed magnesium is).

Diluting Enteral Formulas to “Treat” Diarrhea

As discussed above, diluting enteral formulas to decrease osmolality in patients with normal anatomy flies in the face of GI physiology, and is without evidence. Researchers have shown that hypertonic formulas are tolerated in both healthy subjects³⁴ and in those with impaired GI function.³⁵ Furthermore, the practice of diluting EN can be detrimental to patients as fewer nutrients are provided, and more handling introduces potential contamination with infectious agents. Regardless, with the recent adoption of the ready to hang system, dilution of EN is not possible in the hospitalized setting. Finally, many items commonly provided to our hospitalized patients, including medications, popsicles, fruit juice, soda, and sherbet all have an osmolality much higher than that of EN (Table 3). If high osmolality causes diarrhea, “isotonic” medications, beverages, and oral diets would be needed to prevent diarrhea in all our patients.

There are two circumstances when the dilution of formula may be helpful (primarily in the home setting). With some particularly viscous EN formulas, dilution may be needed. If a highly viscous EN formula is slow to infuse, adding water can thin the formula and enhance flow through small bore feeding tubes. Also, in some patients with higher fluid requirements, water can be added to the EN formula and the mixture run at a higher infusion rate to provide additional hydration. This will decrease the burden of large, frequent water flushes and decrease caregiver time.

Diarrhea is seen in EN-fed patients for a variety of reasons, but EN is very rarely, if ever, the cause. Risk factors other than the enteral formula should be explored including: medications, infectious etiologies, underlying disease state, GI anatomy, and even constipation (stooling around an impaction) in susceptible individuals.¹¹ These issues should be addressed and appropriate steps taken before reducing or suspending enteral feeding. Management of diarrhea in EN-fed patients requires a systematic approach to identify and remove risk factors where possible.6 (Table 4). Ferrie decreased the incidence of diarrhea in critically ill patients from 37% to 24% by careful attention and monitoring of factors known to cause or aggravate diarrhea.36 Once infectious or other etiologies have been ruled out, anti-diarrheal agents can be initiated to improve patient comfort and protect from skin breakdown. Diarrhea as a symptom does not indicate the need for cessation of EN.

Nausea, Vomiting, Abdominal (or any) Pain

It is not uncommon for patients in the hospital setting (or any patient with ongoing medical issues) to have nausea, vomiting, or pain. These symptoms often result in inadequate oral intake in patients who are eating. In patients being enterally-fed, these symptoms often cause EN to be held due to a belief that EN is causing the symptoms. In some cases, parenteral nutrition (PN) is initiated. Effective use of medications, such as antiemetics, prokinetics, or analgesia agents, can improve nausea and vomiting, and these modalities should be optimized before surrendering to PN. Of course, the route of medication delivery is an important consideration. For example, oral medications may not be effective if the patient is frequently vomiting. A medication delivered into the stomach will not be utilized if the patient is on gastric suction or is frequently ‘venting’ a gastric tube to relieve nausea. The timing of medications may also be important in these settings (e.g. 1/2 hour before meals to maximize efficacy) and, if so, these instructions should be included in the recommendations and orders.

The Curse of “PRN” Medications

PRN drug use, or medications given when the need arises, traditionally meant “as little as possible.”³⁷ PRN orders are routine in hospital, rehabilitation, and nursing home settings and are the default ordering method in many institutions. It has been reported that 35-60% of medication orders are PRN.^38,39 Many patients have suffered at the mercy of these “PRN” orders, as no medication is beneficial if not received by the patient. There is a paucity of data regarding PRN medications and how often they are actually given.^39-41There are numerous reasons that PRN orders may not be given: patient does not (or cannot) complain of symptoms routinely, patient does not know meds are available to them (let alone know how to pronounce them), nurses do not get to fully assess the patient’s symptoms, or nurses just run out of time to give PRN meds. A Cochrane review was unable to find any trials comparing scheduled dosing with giving the same medication only “when needed”.40 One study investigated the non-use of PRN medications in a hospital-affiliated with a large mid-western university and found that 62% were unused (4793 of 7735 PRN orders).³⁸ Non-use by service category was also assessed, revealing that cardiovascular surgery had the highest laxative prescribing rate (almost 100% of patients), yet 89% went unused. The percent of all PRN orders unused ranged from a low of 50% for renal transplant to a high of 81% for ophthalmology. In another study of PRN orders for acute pain management following laryngectomy, 68% of patients met the recommended minimum post-op dosing guidelines for pain, yet none of the patients received the intended dose during a 24 hour period while hospitalized.⁴¹ Of the 13 patients (35%) whose physicians were contacted because of inadequate pain relief, only 8 patients (22%) had their narcotic dose increased appropriately. Finally, in a study of children undergoing various elective surgeries, the authors verified that nurses administered 20% of the non-narcotics available under PRN orders, but only 10% of the available narcotics.³⁷

In patients with ongoing symptoms that prevent consistent delivery of EN, it is important to ensure that medications to relieve such symptoms are actually being received by the patient. Always look to doses received, not just ordered. If the patient is not receiving the medication, it is important to find out why — is it being refused? Or, is the medication ordered only as a “PRN”? It may be important to explain to the patient the benefit of the medication, discuss with nursing to determine why it is not being given, or recommend to the primary team that the medication be changed from PRN to scheduled dosing. With some medications, it may be important to go one step further and ensure it is scheduled at specific times. It takes a village to get our patients safely and comfortably EN-fed through a hospitalization.

Constipation

Constipation is a frequent problem in hospitalized patients and is associated with abdominal discomfort, distension, small bowel bacterial overgrowth, poor tolerance of EN, confusion, intestinal obstruction, vomiting, and increased intra-abdominal pressure (which can impact respiratory function).^42,43 Constipation has many possible causes (Table 5). In patients with significant constipation (especially rectal distension), abdominal distension, as well as delayed gastric emptying, can occur due to the recto-esophagogastric reflex.⁴⁴ In more than one study, constipation was reported more frequently than diarrhea in patients fed exclusively by EN.^17,45 Another study in cancer patients indicated that symptoms of constipation cause more distress than symptoms of pain.⁴⁶ Modern definitions define constipation as a poly-symptomatic disorder including various aspects of disturbed defecation. Despite being such a common problem, constipation is often overlooked.^42,47,48 While constipation in the EN-fed patient has often been referred to as a “complication” of EN, it is not possible for EN to cause constipation. Constipation in any patient is, pure and simple, due to an underlying condition and is often worsened by a lack of attention from the healthcare team to this issue.

One common intervention to “treat” constipation is to use a fiber-containing EN. However, fiber is no panacea.⁴⁹ In one study of critically ill patients, constipation was observed as follows: fiber-free EN – the most widely used – (60% constipated), fiber-containing EN (51% constipated), both types used (85% constipated).⁴³ See Table 6 for suggested guidelines to prevent and treat constipation.

Can Dehydration Cause Constipation?

Another myth that persists today is that dehydration causes constipation.⁵⁰ Dr. Lawrence Schiller, a gastroenterologist affiliated with Baylor University Medical Center in Dallas, Texas, with years of clinical experience and numerous publications on the topic of both constipation and diarrhea, explained this common assumption this way:

“There is no support for this notion. The observation may be valid (dehydration and constipation coexist more than you would expect by chance), but it is not that dehydration causes constipation. More likely some factor leads to both dehydration and constipation. For instance, someone who is very ill may not drink much water, but they also are not eating so the main stimulus for colon motility (gastrocolic reflex-the stimulation of colonic contractions after food ingestion resulting in a bowel movement a short time after eating) is absent. Because the gut mucosa beyond the stomach is so permeable to water, there will always be “enough” intraluminal water for normal function, even if there is a total body water deficit. Electrolyte disorders that may accompany dehydration (e.g., hypercalcemia) may exaggerate constipation, but the water deficit is not the primary driver of the bowel symptoms.”

OTHER FACTORS GETTING IN THE WAY

Initiation & Progression

Initiation and advancement of EN varies among facilities (see Table 7 for one institution’s EN initiation protocol). There are no prospective randomized studies to determine the optimal rate to initiate feeding or how quickly to advance. Recommendations for initiation of continuous EN generally start at 20-50mL/hour, and advance by 10-25mL every 4-24 hours. Intermittent or bolus feedings protocols generally start at 120mL every 4 hours, and advance by 30-60mL every 8-12 hours.⁵¹ The results of a recent survey of dietitians in the United Kingdom (n = 606), demonstrated that 65% of respondents reported most commonly using a start rate of 24-49mL/hour, with 50-74mL/hour being the next most common initiation range.⁵² A significant association between the number of years in clinical practice and start rate was found–with those having more clinical experience using a higher start rate.

Extremely slow protocols for EN advancement can lead to decreased nutrition provided to patients. When one considers the actual amount of EN that is provided at a typical flow rate (for example, 60mL/hour equals 1/4 cup delivered over an hour), these advancement protocols seem very conservative. Over the years, various researchers have demonstrated that rates anywhere from 87mL/hour³⁴ to 100-150mL/hour.53 are generally well tolerated. In fact, in two small studies (6-9 subjects), Heitkemper et al demonstrated that subjects tolerated gastrically infused full strength, hypertonic EN at rates of 30-60mL/minute (yes, mL/minute) up to a total of 500mL and 750mL.^54,55 This translates into 500-750mL being infused over 8-25 minutes. Only at a rate of 85mL/minute did subjects experience GI discomfort.54

Although data are sparse on initiating patients at goal flow rates, in addition to the studies above, Taylor et al. compared two different EN starting regimens in 82 head-injured patients.⁵⁶ The two groups were either started at a goal rate (90mL/hour) or with a starter regimen of 15mL/hour advancing every 8 hours as tolerated to 30, 60, and then 90mL/hour based on energy requirements. The 90mL/hour group (treatment) included both small bowel and gastrically-fed patients; the starter group enlisted only gastrically-fed patients. There were no significant differences in infectious complications or pneumonias (including aspiration pneumonia). At discharge, patients going home on pump feedings from University of Virginia Health System (UVAHS) are advised that they can advance their EN rate by 5-10mL/hour every three days or so, until they are running the set number of cans over the number of hours that suits them (or until further advancement is not tolerated). In general, 120-150mL/hour is an acceptable target as long as the patient is “comfortable.” Demonstrating just how much 120mL (1/2 cup) is to patients (using a cup available at bedside) may be a helpful visual. The exception to these instructions are those patients on insulin — coordination with their endocrine team is necessary to adjust insulin as the feeding regimen is changed.

Calculating Run Time for Patients on Continuous Feeding

Because of the many barriers to EN and the lost feeding time that results, patients often do not receive the prescribed goal nutrition. One approach to improve the amount of nutrition delivered is to base flow rate calculations on a less than 24-hour time period.^57-59 For example, at UVAHS, the calculations of goal flow rate for continuously fed patients are calculated based on 22 hours/day for ICU and 20-21 hours for floor patients. The EN orders are then entered as continuous, but at the padded rate to account for the expected EN downtime. EN rates are then modified as needed, depending on the actual “dose received” in the days that follow.

SUMMARY

EN is a safe and effective way to nourish patients unable to eat enough on their own. Many barriers exist in the hospital setting that impede successful EN delivery to patients; however, many of these obstacles are based on the unsupported perception that EN causes GI symptoms. Part two of this series specifically addresses diarrhea, osmolality, infusion rates, nausea, vomiting, and pain as barriers to successful EN, and provides alternative approaches to maximize nutrient delivery in the enterally-fed patient.

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NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #188

FODMAPS Everywhere and Not a Thing to Eat!

July 2019 • Volume XLIII, Issue 7

Amanda Motl,

Nimish Vakil

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Amanda Motl, RD Aurora Medical Center, Summit, WI Nimish Vakil, MD, AGAF, FACG, FASGE University of Wisconsin School of Medicine and Public Health, Madison WI, Aurora Medical Center, Summit WI.

FODMAP is an acronym for fermentable oligosaccharides, disaccharides, monosaccharides and polyols. Dietary restriction of FODMAPs helps patients with the irritable bowel syndrome. Registered dietitians are essential for the education of patients in initial FODMAP restriction, structured re- introduction and final implementation of a personalized diet. Further areas of research include the adverse effects of FODMAP restriction on the microbiome, the effects of long-term FODMAP restriction on nutrition and intestinal health and the possible use of low FODMAP diets in other disease states.

Introduction
FODMAP is an acronym that stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. These are all fermentable short-chain carbohydrates of 3-10 sugars and are commonly found in many everyday foods (Table 1). These are carbohydrates that are poorly absorbed and osmotically active in the small intestine, drawing water into the lumen and fermented by bacteria in the colon producing gas. Dietary restriction of FODMAPs improves symptoms of diarrhea, abdominal pain, distention and bloating in patients with irritable bowel syndrome. A comprehensive review of this subject has recently been published.¹

Carbohydrates and Their Absorption Simple sugars are monosaccharides (glucose, fructose and galactose) and disaccharides (sucrose, lactose, maltose) that are present in milk, fruits, and vegetables that add varying degrees of sweetness to food. Disaccharides consist of two monosaccharides chemically joined together. The important disaccharides are sucrose (table sugar), lactose (milk sugar) and maltose (a product of starch digestion). Sugar alcohols are derivatives of monosaccharides. As with other sugars they taste sweet and are a source of energy, but they provide the same degree of sweetness as sugar with fewer calories and are therefore used as low-calorie sweeteners. They are absorbed more slowly than monosaccharides. Polysaccharides are long chains of monosaccharides. The way the monosaccharides are linked makes them absorbable (starch) or non-absorbable (fiber). Plants store energy as starch, which is a complex carbohydrate made of long chains of monosaccharides. Glycogen is also called animal starch and is used to store energy in humans and other animals. Most glycogen in slaughtered animals deteriorates within 24 hours. Pancreatic amylase breaks starch into smaller units of maltose.

FODMAP Absorption
Most carbohydrate digestion and absorption takes place in the small intestine. All carbohydrates must be broken down into monosaccharides for absorption. A sodium-dependent transporter moves the monosaccharides glucose and galactose into the enterocyte.

Monosaccharides
Fructose is a monosaccharide, which is absorbed in the presence of glucose. Fructose is transported primarily by either GLUT-2 or GLUT-5 carrier proteins across the intestinal epithelium. The GLUT-5 transporter is specific to only fructose, but the GLUT-2 transporter relies on glucose to facilitate passage of fructose.2 Clinical studies have shown that a fructose:glucose ratio of 1:1 is ideal for absorption for fructose; higher proportions of fructose are malabsorbed.3 Approximately half the U.S. population cannot absorb and tolerate > 25 grams of fructose, yet the fructose content of many diets regularly exceeds 50 grams (an amount that 100% of humans cannot absorb), primarily due to the ingestion of sweetened beverages (most often with high fructose corn syrup)^4,5 (Table 2).

Oligosaccharides
Oligosaccharides are carbohydrates, which are made up of 3-10 simple sugars, composed mainly of fructans and galacto-oligosaccharides (GOS). A fructan is a polymer of fructose molecules. Fructans with a short chain length are known as fructo-oligosaccharides. They are poorly absorbed because the human body does not possess the enzyme to break them apart.

Disaccharides
Disaccharides such as lactose are variably absorbed because lactase, the enzyme needed to digest this sugar is genetically determined and absent in some populations (68% of the world’s population is lactase nonpersistent).⁶

Polyols
The last group consists of polyols, which are sugar alcohols that add the taste and texture of sugar with approximately half the number of calories. They are slowly absorbed by passive diffusion. Polyols are sugar alcohols found naturally in some fruits and vegetables (Table 3). They are also widely manufactured and used as artificial sweeteners. Absorption of sugar alcohols is dose dependent and influenced by the molecular size of the individual polyol. Sorbitol intolerance is a common problem in healthy individuals and can cause bloating and abdominal distress.⁷ These symptoms tend to occur with intakes of just 10-20 grams/day; greater amounts of up to 50 grams can have a laxative type effect.8 Sorbitol, mannitol and xylitol are examples of sugar alcohols used as sweeteners. For example, sorbitol is often used in chewing gum, breath mints, candy and many liquid medications such as cough syrups, analgesics, etc. and is an important source of symptoms in some patients. Many commonly used medications contain sorbitol ⁹ (Table 4).

Physiological Effects of FODMAPs
Small Intestine Water Volume
FODMAPs are osmotically active and draw water into the lumen of the small bowel. Using subjects with an ileostomy, a two-fold increase in ileostomy fluid output was demonstrated with the oral administration of fructose and sorbitol.^10,11 The increase in intestinal volume results in distention of the small intestine and can cause pain in patients with visceral hypersensitivity.¹² A scintigraphic study has demonstrated that ingestion of an oral fructose-sorbitol solution reduces transit time from the mouth to the cecum in healthy individuals, without altering gastric emptying; thereby demonstrating increased motility of the small intestine.¹³ An increase in motility in the small intestine contributes to symptoms of diarrhea.

Colonic Gas Production
Colonic bacteria ferment poorly absorbed carbohydrates that reach the colon resulting in the production of methane and hydrogen. Breath testing shows an increase in hydrogen and methane gas production with high FODMAP diets.¹⁴ An increase in colonic gas leads to bloating and distention, and in patients with intestinal hypersensitivity, causes pain. Oligosaccharides have shown a greater fermentative effect than other FODMAPs and MRI studies show greater colonic distension with inulin (a plant polysaccharide) compared to fructose (a monosaccharide).¹⁵

Visceral Hypersensitivity
Fermentation results in the production of short chain fatty acids (SCFAs) in the colon. SCFAs consist of acetate, propionate, and butyrate and serve as a fuel source for colonocytes. They also play a role in lipid, glucose, and cholesterol metabolism and are important for intestinal health.¹⁶ High FODMAP diets increase serum levels of lipopolysaccharides leading to gut permeability, intestinal inflammation, and visceral hypersensitivity.¹⁷ This increases the likelihood of developing pain with intestinal distention.

Gut Microbiome
Oligosaccharides are known for their prebiotic effect on the body. A restriction of these carbohydrates with a low FODMAP diet has been shown to reduce levels of luminal bifidobacter, which has been well established in contributing positive health benefits including improved immune function.^14,18 A 3-4 week duration of FODMAP restriction resulted in 6-fold reduction in bifidobacteria (a desirable bacterial species in the microbiome) compared to controls.¹⁹ Another recent study also showed a change in the bacterial content of the intestinal microbiome after short-term administration of a low FODMAP diet.20 Co-administration of a probiotic while on a low FODMAP diet restored concentrations of bifidobacter along with providing symptom relief.²¹

Effect of Low FODMAP Diets on the Metabolome
Foods result in the generation of small-molecule chemicals in the body that have physiological effects. These chemicals are called the food-induced metabolome. Low FODMAP diets have an effect on the metabolome. Three active food-induced chemicals (histamine, p-hydroxybenzoic acid, and azelaic acid) were studied in an experimental intervention using a high FODMAP and a low FODMAP diet. Histamine, a measure of immune activation, was decreased 8-fold on the low FODMAP diet.²² Histamine may have a role in IBS as histamine levels have been shown to be elevated in these patients.²³

Use in Gastrointestinal Disorders
Irritable Bowel Syndrome (IBS)
A meta-analysis of short-term studies on low FODMAP diets in IBS found 6 randomized controlled trials and 16 non-randomized trials demonstrating substantial improvements in IBS symptoms with a low FODMAP diet.24 A more recent meta-analysis found seven randomized controlled trials comparing a low FODMAP diet with control interventions. A low FODMAP diet was associated with reduced global symptoms compared with control interventions, but the quality of the data was low.²⁵

Inflammatory Bowel Disease (IBD)
Functional gastrointestinal symptoms are present in a proportion of patients with inflammatory bowel disease. Functional symptoms are more likely in patients with Crohn’s disease compared to patients with ulcerative colitis perhaps due to disease location.²⁶ There is some evidence to support use of a low FODMAP diet in patients with IBD in whom the inflammatory bowel disease is controlled, but symptoms persist. Improvements were seen in stool consistency and frequency along with decreased severity of abdominal pain, bloating, and flatulence.²⁷

Celiac Disease on a Gluten Free Diet (GFD)
Life-long adherence to a gluten-free diet is the only current treatment for patients with celiac disease. Despite strict adherence to a gluten-free diet, symptoms are reported by 47% of patients with celiac disease.²⁸ A randomized, controlled trial of patients with celiac disease on a gluten free, low FODMAP diet showed significant improvement in functional gastrointestinal symptoms and psychological health scores.²⁹

Non-Celiac Gluten Sensitivity
Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in the absence of celiac disease. Wheat is a very important source of fructans in the U.S. diet. A recent study aimed to evaluate the effects of gluten and fructans on the genesis of symptoms in patients with non-celiac gluten sensitivity. In a double-blind trial, patients with non-celiac gluten sensitivity and IBS were given a low FODMAP diet for 2 weeks followed by a high-gluten, low-gluten and a control period of whey protein.³⁰ Symptoms improved on the low FODMAP diet, but worsened equally when gluten or whey protein was added to the diet suggesting that the cause of food sensitivity may be multi-factorial. Skodje et al. studied subjects who did not have celiac disease, but were on a self-imposed gluten-free diet.³⁰ These individuals were administered diets containing gluten, fructans or placebo concealed in muesli bars for 7 days. After a wash-out period, the subjects were re-randomized until all three diets were administered to all subjects. Symptoms of bloating and overall symptoms of IBS worsened during fructan administration, but the effect of gluten containing diets was similar to placebo. This trial suggests that fructans may have a role in the development of symptoms and therefore a low FODMAP diet could help these patients. Another recent study evaluated the effect of a low FODMAP compared to a gluten-free diet on clinical symptoms, psychological well being, intestinal inflammation and integrity, and stool microbiota in subjects with non-celiac gluten sensitivity. Both the low FODMAP diet and the gluten free diet resulted in a significant improvement in symptoms in patients with non-celiac gluten sensitivity. There was a decrease in duodenal intraepithelial lymphocytes and mucin-producing Goblet cells after administration of a gluten free diet. Significant changes were seen in the stool microbiota composition in patients with non-celiac gluten sensitivity and controls. This study suggests that symptom generation may be multi-factorial in patients with non-celiac gluten sensitivity.³¹

Low FODMAP Diet Implementation
A practical guide to implement the FODMAP diet in clinical practice has recently been published and this subject is only briefly covered here.³²

Elimination
The elimination phase is the first of three phases of the low FODMAP diet (Table 5). It is during this time that patients restrict all high FODMAP foods from the diet for 2-6 weeks. The goal during this phase is to determine if there is sensitivity to FODMAPs because not all patients will elicit a response. A biomarker may be helpful to identify patients who would benefit from a low FODMAP diet. In one study, measurement of volatile organic compounds in stool predicted with 97% accuracy whether an IBS patient responded to a low FODMAP diet.³³ Further validation of this biomarker is needed. A number of resources are listed in Table 6 and can help patients through this phase.

Re-introduction
The low FODMAP diet is too restrictive for long-term use. Therefore, the next step is to systematically challenge the patient with each FODMAP component. The general principle is to introduce small amounts of one group and gradually increase the dose on day two and three if the food is tolerated. If symptoms develop, the challenge is stopped and a 3-4 day wash out period is started until symptoms resolve. If no symptoms are observed, the next FODMAP challenge begins. This process typically lasts 6-8 weeks. No evidence-based guidance is available at this time, but Table 7 shows our approach to the re-introduction of foods.

Maintenance
The final phase of the diet modification is long-term adherence to a personalized FODMAP plan. The individualized plan is created based on the results of the previous phase. FODMAPs that trigger symptoms are limited, but the others are added back to the diet.

FODMAPS and Enteral Feeding
FODMAPs may have an important role in adverse effects caused by enteral feeding. In a retrospective study of patients with diarrhea caused by enteral feeding in Australia, the FODMAP content of the enteral feeding ranged from 10.6 to 36.5 g ⁄ day. A low FODMAP enteral formula was associated with a five-fold reduction in diarrhea rates.³⁴ A randomized, controlled trial of a low, moderate, and high FODMAP enteral feeding was conducted in Korea. There was a significant reduction in diarrhea and improvement in nutritional parameters and clinical outcome in patients randomized to the low FODMAP enteral feeding formula.³⁵ Quantifying FODMAPs in enteral formulas has proved to be difficult because of the interference with in vitro assays of fructans and raffinose caused by the maltodextrin content of the formula.36 Therefore, there is a no ready source for the FODMAP content of enteral feeding formulations in the United States. However, in symptomatic patients, a trial of FOS, fiber, and inulin free formulas may be beneficial.

The Role of a Dietitian
A low FODMAP diet is restrictive and can be confusing to implement without guidance. Patients benefit from instruction provided by a dietitian who specializes in GI nutrition and is familiar with the low FODMAP diet.³⁷ A recent survey of over 1,500 gastroenterologists suggested that most felt that dietary intervention was as good, or better, than other available treatments for IBS.3⁸ The survey also demonstrated that only a small portion of gastroenterologists refer patients to a dietitian with specialized GI training despite the fact that the majority believed that GI trained dietitians would be of benefit to their patients. This may be related to the lack of access to dietitians with specialized training. Resources for low FODMAP diets are becoming more available to the general public and there is a tendency to give the patient a handout and refer them to on-line resources (Table 6). We gave up this approach in our department when patient dissatisfaction and a poor response to dietary intervention lead us to re-evaluate it. All our patients are now instructed by a registered dietitian and are followed until a personalized diet plan is developed. The dietitian may also have a role in monitoring the nutritional status of patients who are on low FODMAP restricted diets for long periods of time.
Long-Term Risks and Unanswered Questions Dietary intervention carries the risk of being considered “all-natural” and risk-free. Limited data are available on the nutritional consequences of prolonged restriction of FODMAP s in the diet. Changes in the microbiome and in the composition of gut content may have adverse effects on health. For example, short chain fatty acids are decreased in the colon on low FODMAP diets. Short chain fatty acids are trophic to the colon mucosa and essential for intestinal health.

CONCLUSION
A low FODMAP diet can be an effective treatment for IBS, but increasing evidence suggests a possible use in symptomatic patients with quiescent inflammatory bowel disease, non-celiac gluten sensitivity, and celiac disease with persistent symptoms on a gluten-free diet and normal celiac serology. In some patients, FODMAPs in enteral feeding formulas can cause bloating and diarrhea in tube-fed patients. Registered dietitians are essential for the education of patients in initial FODMAP restriction, structured re-introduction and final implementation of a personalized diet. Further areas of research include the adverse effects of FODMAP restriction on the microbiome, the effects of long-term FODMAP restriction on nutrition and intestinal health and the possible use of low FODMAP diets in other disease states.

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Naturlax: Your All-Natural, Sugar-Free Fiber Supplement

July 2019 • Volume XLIII, Issue 7

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Naturlax is an all-natural fiber supplement that contains no artificial ingredients and comes in over 80 delicious flavors.
ORANGE, CA–Naturlax, a fiber supplement company, offers an all-natural, sugar-free psyllium fiber supplement available in over 80 unique flavors.
Although other fiber supplement brands may have sufficient fiber per serving, Naturlax psyllium husk supplement is 100% free of any artificial ingredients. Naturlax focuses on being the premiere all-natural, sugar-free fiber supplement for young and old patients alike. Unlike traditional flavors such as orange and berry, Naturlax offers over 80 unique, gourmet flavors completely derived from all-natural fruits, vegetables, and plant extracts.

Active ingredient is psyllium husk
Over 80 delicious, all-natural flavors
Sugar-free, sweetened with our proprietary blend of stevia and erythritol

Naturlax is a family-owned and run company located in Orange, California that specializes in providing an array of psyllium fiber flavor options because everyone deserves a fiber supplement suited to their own unique taste. Naturlax ensures that all of their products and ingredients are of the highest quality so that we can provide superior natural supplements that support a healthy lifestyle.

Medical Bulletin Board

Louisiana Launches Hepatitis C Innovative Payment Model with Asegua Therapeutics, Aiming to Eliminate the Disease

July 2019 • Volume XLIII, Issue 7

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Modified Subscription Arrangement Reflects Shared Commitment to Significantly Increase Access to Hepatitis C Cures in Louisiana; State’s Goal is to Serve 31,000 Patients by End of 2024.
Baton Rouge, LA and Foster City, CA – Governor John Bel Edwards joined Secretary Rebekah Gee of the Louisiana Department of Health, Secretary James LeBlanc of the Louisiana Department of Corrections, and Asegua Therapeutics LLC, a wholly-owned subsidiary of Gilead Sciences, Inc. (Nasdaq: GILD), to announce a deal that will allow the implementation of an innovative payment model for hepatitis C treatment, part of Louisiana’s plan to eliminate the disease.

“This new model has the potential to save many lives and improve the health of our citizens. It is an important day for our state, for our partner Asegua Therapeutics, for providers, but most importantly for the patients and their families who will benefit from treatment,” said Governor Edwards. “Asegua was willing to come to the table to work with us to help Louisiana residents and we are pleased to initiate this five year partnership. Ultimately, our goal is to eliminate this disease in Louisiana, and we have taken a big step forward in that effort.”

In the United States, hepatitis C kills more people than all other infectious diseases combined. At least 39,000 people in Louisiana’s Medicaid program and prison system suffer from hepatitis C infection.

“An elimination plan and innovative payment model will ensure that we can cure this deadly disease and prevent long-term illness and disability in those who have it,” said Dr. Rebekah Gee, secretary of the Louisiana Department of Health. “The Department of Health’s goal is to treat at least 31,000 people by the end of 2024 and eventually eliminate this disease.”
After extensive research and work with policy experts across the nation, the Department of Health released a solicitation of offers in January of 2019 in search of a pharmaceutical company willing to partner with Louisiana on a subscription model. Asegua Therapeutics was announced as the selected partner in April, and through subsequent discussions the parties have agreed to a modified model.

“We are pleased that Asegua has the courage to be a pioneer and chart a new path forward that will allow us to save many lives and improve the health of our citizens,” added Gee.

The innovative payment model for Louisiana addresses the needs of patients and joins the goals of both Louisiana and Asegua to extend a cure to those in need.

“This partnership will have a direct and immediate impact on the most vulnerable populations with hepatitis C – people who are on Medicaid or who receive care through the state corrections system. These populations are disproportionately affected by hepatitis C and often face the greatest difficulty in accessing care,” said Gregg Alton, Chief Patient Officer at Gilead Sciences. “We are committed to supporting efforts to eliminate hepatitis C in communities around the world and are excited to partner with the visionary leaders in Louisiana to make this public health opportunity a reality in this state.”

The innovative payment model allows the state to purchase an unlimited amount of Asegua’s direct-acting antiviral medication, the authorized generic of Epclusa® (sofosbuvir/velpatasvir) to treat patients within Louisiana’s Medicaid and Department of Corrections populations and caps the State’s medication costs.

“With this model to purchase hepatitis C medications, we can cure those within the state facilities who have this life-threatening illness and prevent the spread of the illness within our facilities,” said James LeBlanc, secretary of the Louisiana Department of Corrections. “We will also work closely with the Department of Health to implement a plan to screen and treat the local level population either while incarcerated or upon release into supervision. Most importantly, we can make sure these men and women have an opportunity to be even more successful and healthy when they return to their communities.”

The Department of Health and Asegua completed and signed a formal contract for the purchase of Asegua’s hepatitis C medication, the authorized generic of Epclusa, over five years, and for people enrolled in the Medicaid program and incarcerated people in Louisiana. The Department of Health continues to implement an elimination plan that engages partners across the state to educate the public on the availability of a cure and reach out to high-risk populations for screenings; connect people living with hepatitis C to care; expand provider capacity; and establish partnership across the state to eliminate hepatitis C in Louisiana.

About Louisiana Department of Health
The Louisiana Department of Health strives to protect and promote health statewide and to ensure access to medical, preventive and rehabilitative services for all state residents. The Louisiana Department of Health includes the Office of Public Health, Office of Aging & Adult Services, Office of Behavioral Health, Office for Citizens with Developmental Disabilities, and Healthy Louisiana (Medicaid).

Visit LDH Website

About Asegua Therapeutics
Asegua Therapeutics is a wholly-owned subsidiary of Gilead Sciences, Inc. Gilead Sciences is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements
This press release includes forward-looking statements related to Asegua Therapeutics, a subsidiary of Gilead Sciences, Inc., within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that the parties not may not realize the potential benefits of this partnership. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information, please visit: gilead. com or call Gilead Public Affairs at: 1-800-GILEAD-5 or 1-650-574-3000

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

CASE

INTRODUCTION

PATIENT’S SYMPTOMS AS A BARRIER

Diarrhea

Malabsorption

Contributions of Medications

Antibiotic-Associated Diarrhea

Hypoalbuminemia

Osmolality or Hypertonicity

Diluting Enteral Formulas to “Treat” Diarrhea

Nausea, Vomiting, Abdominal (or any) Pain

The Curse of “PRN” Medications

Constipation

Can Dehydration Cause Constipation?

OTHER FACTORS GETTING IN THE WAY

Initiation & Progression

Calculating Run Time for Patients on Continuous Feeding

SUMMARY

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

RESULTS
Demographics