Optimizing Enteral Nutrition Support for Adult Patients with Fat Malabsorption

Publication Date: September 18, 2020
Last Updated: November 3, 2022

Overview and Prevalence

Overview and Prevalence

Key Point

  • Malabsorptive diarrhea is most commonly related to malabsorption of fat.

Prevalence of Target Diseases

  • Diarrhea in non-hospitalized patients is common, affecting as much as 5% of the population. In the context of concurrent alarm signs (weight loss and vitamin deficiency in particular) and an underlying diagnosis involving the gastrointestinal (GI) tract, malabsorption should be considered.
  • Diarrhea associated with hospitalization is common and may occur in up to 12-32% of patients. This can be due to a multitude of causes and frequently relates to medication side effects.
    • Diarrhea is often incorrectly implicated as a side effect of enteral nutrition and may result in inadequate nutrition support for hospitalized patients.
  • In critically ill patients, malabsorption can be associated with fat or carbohydrate; however, it is unknown if this is long-standing or clinically important.
    • Fat malabsorption: Critical illness itself has been implicated in malabsorption associated directly with critically ill patients (e.g. septic shock). However, malabsorption may also occur for many reasons in less acutely ill patients.
      • Some studies have suggested that as many as 50% of patients have relative pancreatic insufficiency during the course of critical illness.
      • Irregularities of bile salt secretion may also contribute.
    • Carbohydrate malabsorption: This may occur due to downregulation of active transporters along the mucosal brush border. This is often a less clear contributor than fat malabsorption.
  • When considering malabsorption as a cause of diarrhea, have a rational thought process for evaluating the GI tract (Table 1) and potential causes of fat malabsorption (Table 2).

Table 1. Basic Approach to Assessing Diarrhea and Concern for Malabsorption

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FIRST Carefully evaluate for common causes of diarrhea (e.g., medication side effects, sugar alcohols from liquid medication, and C. difficile) and, finally, malabsorption.
Second Classify diarrhea as inflammatory, secretory, or malabsorptive.
Third Consider underlying GI disorders (pancreatic or cholestatic process, celiac disease, microscopic colitis, IBD, small intestinal bacterial overgrowth).
Fourth Evaluate for fat malabsorption (see Table 3).

Table 2. Potential Causes of Fat Malabsorption

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Bile Salt Deficiency-Related Diagnoses
Impaired/inadequate mixing of bile with fat
  • Biliary obstruction
  • Surgical diversion (e.g., gastric bypass and Whipple procedure)
  • Percutaneous biliary drains
  • Post-cholecystectomy
Impaired synthesis/inadequate production
  • Cirrhosis
  • Chronic cholestasis
  • Ileal disease
  • Ileal resection (typically >100 cm)
  • Bacterial overgrowth
Pancreatic Insufficiency/Deficiency
Failure to produce pancreatic enzymes
  • Pancreatitis
  • Cystic fibrosis
  • Celiac sprue
  • Diabetes
  • Surgical pancreatectomy
  • Normal aging
Failure to deliver pancreatic enzymes
  • Benign pancreatic duct obstruction
  • Malignant duct obstructions
  • Surgical diversions
  • Bowel obstruction distal to pancreatic secretions
Inactivation of pancreatic enzymes
  • Gastric hypersecretion first 6–12 months of short bowel syndrome due to resection
  • Zollinger Ellison syndrome
KEY POINT: Infections associated with diarrhea are exceedingly rare causes of malabsorptive diarrhea. In the inpatient setting, there is a 6% yield of positive tests with significant concern for false positive tests. Clostridium difficile-associated diarrhea however, should always be ruled out.

Diagnosing Fat Malabsorption

Diagnosing Fat Malabsorption

  • While malabsorption may contribute to diarrhea, inflammatory, and secretory causes of diarrhea should also be considered and excluded. If there is a question of secretory or inflammatory diarrhea, an NPO trial is a valuable test. If diarrhea persists in a patient who is NPO, further evaluation should be dedicated to secretory and inflammatory causes of diarrhea.
  • KEY POINT: Nutritionally significant malabsorption of fat can sometimes occur without overt diarrhea—i.e., patients can be constipated.
  • See Table 3 for a summary of clinical testing for fat malabsorption.

Table 3. Tests for Fat Malabsorption

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Test Procedure Advantages Limitations
Qualitative Fecal Fat
(“spot or random check”)		 Single stool specimen is assessed for fat content. Easy—requires only one small stool sample. Positive result is unable to inform the extent of malabsorption.

Negative result does not rule out malabsorption.

Does not identify cause of fat malabsorption.

Patient needs to ingest at least 60 g fat/day.
Quantitative Fecal Fat

Fat malabsorption confirmed if there is >7 g stool fat on 100 g fat/day diet or >7% of fat intake of the recorded diet		 Complete a diet record of all oral and enteral nutrition beginning the day before the stool collection and continue throughout the testing period to assess grams of fat ingested in order to compare with that lost in stool.

Collect and keep in a cool place all stool over a 72-hour period for assessment of fat content. Shorter 24- and 48-hour studies are less ideal but may still be useful if fat malabsorption is documented and may be more easily performed in the inpatient setting for patients who cannot stay 3 days.		 Demonstrates extent of malabsorption, comparing fat intake vs. output.

Can demonstrate adequacy of therapy for patients already on pancreatic enzyme replacement therapy (PERT) or semi-elemental EN.		 Cumbersome, requiring accurate diet record and stool collection from 1–3 days.

Does not distinguish between causes of fat malabsorption.

Patients need to be ingesting enough fat (ideally 100 g fat/day), but at least 50 g/day minimum.
Fecal Elastase (FE-1)

Mild to moderate EPI = <200 μg/g

Severe EPI = <100 μg/g		 Elastase is secreted by pancreas and is stable in the GI tract. If present, it will not be degraded so its presence in the stool reflects general pancreas enzyme secretion.

Measurement is from a single stool sample using an enzyme-linked immunosorbent assay (ELISA) and does NOT require dietary fat intake.		 Easy—requires a small stool sample.

Do not have to stop PERT for test (only when monoclonal ELISA testing is used).

No special diet is required.

FE-1 is specific to EPI.		 Watery stools cause false positive result due to dilutional effect.

Will not reveal other non-EPI related causes of fat malabsorption.
Bile Salt Deficiency There is limited testing specific to bile salt deficiency. Most commonly, this is a clinical diagnosis in the context of fat malabsorption and related diagnoses (see Table 2).
KEY POINT: Suboptimal studies can sometimes be interpreted. A high % of fat lost in the stool could still be considered positive if <50g of fat consumed if there is an accurate record of grams of fat ingested.
  • Malabsorption is often evident in a patient’s clinical and nutrition presentation (Tables 4 & 5).

Table 4. Common Symptoms and Signs of Fat Malabsorption

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Abdominal symptoms
  • Greasy, large-volume, foul-smelling stools, steatorrhea
  • Diarrhea, gas, bloating, cramping, abdominal distension, fecal urgency
Biochemical
  • Fat-soluble vitamin deficiency
Nutritional
  • Persistent or unexplained weight loss
  • Inadequate weight gain despite adequate nutrient intake
  • When performing a comprehensive nutrition assessment of a patient with fat malabsorption, consider evaluating serum levels and physical signs of fat-soluble vitamin deficiencies. Please note that serum levels may not be accurate in cases of acute illness or inflammation.

Table 5. Vitamin Deficiencies Associated with Fat Malabsorption

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Vitamin Signs of deficiency
Vitamin A
  • Impaired night vision
  • Dry eyes
  • Scaly, nodular rash
  • Hyperkeratosis at the hair follicle
  • Frequent infections
Vitamin D
  • Osteoporosis or osteopenia
Vitamin E
  • Hemolysis
  • Ataxia
  • Muscle weakness and areflexia
Vitamin K
  • Bleeding
  • Petechiae and purpura

Enteral Nutrition Options in the Patient with Fat Malabsorption

Enteral Nutrition Options in the Patient with Fat Malabsorption

Pancreatic enzymes and bile salts are required for optimal absorption of fat in the diet or enteral feedings.

  1. If a patient receiving enteral nutrition has fat malabsorption due to pancreatic insufficiency:
    1. Consider enteral formula selection (Table 6).
    2. Consider pancreatic enzyme replacement (Tables 7, 8).
  2. If a patient receiving enteral nutrition has fat malabsorption due to bile salt deficiency:
    1. Consider enteral formula selection (defined as ideally <60 g fat/day) (Table 6).
    2. There is no bile salt replacer available that has been shown to be clinically effective.
    3. If patient has an external biliary drain and is losing a significant volume of bile salts, the patient will need a low-fat formula (Table 6).
    4. In select patients, reinfusing bile may be an option if patient has an external biliary drain & jejunal access (NOT if biliary drainage is infected).
    5. KEY POINT: Medium chain triglycerides (MCT) can be absorbed across the brush border. However, in the setting of fat malabsorption, despite interventions, absorption will still be imperfect. Excessive doses of MCT can overwhelm mucosal receptors requiring MCT to be absorbed using the same pathway as long chain fat. Hence, pancreatic enzyme dosing must be based on total grams of fat intake. Also, MCT will not provide essential fatty acids (EFA); consider evaluating patient for EFA deficiency if signs and symptoms develop.

Table 6. Fat Content of Elemental, Semi-Elemental, and Low-Fat Enteral Formulas

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Formula Calories/mL g Fat/liter % MCT mL/1000 kcal g fat/1000 kcal g fat/2000 kcal
Semi-elemental (caution: despite MCT content, total fat content may be high)
Peptamen 1.0 39 70 1000 39 78
Peptamen 1.5 1.5 56 70 666 37 75
Peptamen Intense VHP 1.0 38 50 1000 38 76
Perative 1.3 37 40 769 29 57
Pivot 1.5 1.5 51 20 666 34 68
Vital 1.0 1.0 38 47 1000 38 76
Vital AF 1.2 1.2 54 45 833 29 58
Vital 1.5 1.5 57 47 666 38 76
Vital HP 1.0 23 50 1000 23 46
Strict elemental (very low fat)
Vivonex RTF 1.0 12 40 1000 12 23
Vivonex T.E.N. Powder 1.0 3 0 1000 3 6
Vivonex Plus Powder 1.0 25 0 1000 25 50
Low-Fat Standard Polymeric (criteria for low fat <60 g fat/day)
Promote 1.0 26 19 1000 26 52
Replete 1.0 34 20 1000 34 68
Boost Original 1.0 25 0 1000 25 50
Boost High Protein 1.0 25 0 1000 25 50
Isosource High Nitrogen 1.2 40 20 1000 32 64
Osmolite 1.2 1.2 39 20 833 32 64
Osmolite 1.5 1.5 49 19 666 32 64
Mixed Formulas (1:1 mix)
Promote/Vivonex RTF 1.0 19 26 1000 19 38
Peptamen 1.5/Vivonex RTF 1.25 34 66 800 27 54
Perative/Promote 1.15 32 31 869 28 55
Vital HP/Vivonex RTF 1.0 17 45 1000 17 35
Osmolite 1.5/Vivonex RTF 1.25 30 30 800 24 48

Table 7. Pancreatic Lipase Dosing for Adults Based on Dietary Fat Content

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Lipase Dosing Comments
500–4000 lipase units/g dietary fat infused
  • For suspected or mild pancreatic insufficiency, start with 500 lipase units/g fat. If clinical response is not sufficient, increase weekly by 500 lipase units/g fat until response is satisfactory.
  • For known moderate to severe pancreatic insufficiency, start with 2000 lipase units/g fat.
  • If patient is receiving what should be adequate enzymes and is not responding, see pancreatic enzyme replacement tips and trouble-shooting (Table 12).

Table 8. Oral Pancreatic Enzymes & Dosage Units

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Form Product Manufacturer Lipase units
Enteric-coated capsule contents (acid suppression may be required if the pancreas is so compromised that bicarbonate secretion is diminished or absent to alkalinize gastric secretion from the stomach) Creon AbbVie
  • 3000
  • 6000
  • 12,000
  • 24,000
  • 36,000
Pancreaze Vivus
  • 2600
  • 4200
  • 10,500
  • 16,800
  • 21,000
Pertzye Digestive Care, Inc
  • 4000
  • 8000
  • 16,000
  • 24,000
Zenpep Nestlé Health Science
  • 3000
  • 5000
  • 10,000
  • 15,000
  • 20,000
  • 25,000
  • 40,000
Non-enteric coated tablet (acid suppression is required) Viokace Nestlé Health Science
  • 10,440
  • 20,880
Notes:

• Although oral pancreatic enzymes also include protease and amylase, clinicians typically dose based on lipase units.

• Oral pancreatic enzymes are derived from porcine sources and should be used with caution in individuals with pork allergy.

Pancreatic Enzyme Delivery with Enteral Nutrition

  • There are two FDA-approved options for delivery of pancreatic enzymes with EN as well as other non-FDA approved anecdotal methods (Table 9). Advantages and disadvantages of those options are listed in Table 10. Table 12 highlights factors that affect pancreatic enzyme efficacy.
  • PERT administration with enteric nutrition requires careful consideration of the challenges:
    • Challenge 1: Ensure nurse/caregiver has clear understanding of the process.
    • Challenge 2: Ensure adequate mixing between PERT and fat content particularly during long periods of continuous EN infusion.
    • Challenge 3: Avoid clogging and damage to feeding tubes.
  • Novel products as well as creative use of standard enzyme replacement capsules have been used to overcome these issues.

Table 9A. Three Pancreatic Enzyme Delivery Options for EN

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Method 1: FDA-Approved Lipase Cartridge for Continuous Enteral Feedings
RELiZORB (Alcresta Therapeutics)
  • FDA approved for use in pediatric patients (ages 5 years and above) and adults
  • Lipase mixes with enteral nutrition in the delivery cartridge NOT the lumen of the GI tract.
  • Formulas containing insoluble fiber cannot be used since they will clog the cartridge. See website for compatible formulas (https://www.relizorb.com/docs/pdfs/Compatible-Formulas-and-Pumps.pdf)
  • One cartridge is needed for every 500 mL of EN formula.
  • Feeding pumps must be set at a flow rate of at least 10 mL/hr for single cartridge setup and 24 mL/hr in tandem configuration.
  • Maximum flow rate is 120 mL/hr
Method 2: FDA-Approved Delivery of Oral Pancreatic Enzymes for Enteral Feedings via a Gastrostomy Tube*
Pertzye (4000 USP lipase units - Digestive Care, Inc.)
  • Pertzye is the only oral pancreatic enzyme with US FDA approval for gastrostomy (G) tube administration. http://www.digestivecare.com/PDFs/DCI_G-Tube2017.pdf
  • G-tube administration should only be performed with the contents of one or two 4,000 USP lipase unit capsules.
  • Administer with soft foods with a pH of ≤4.0 via a G-tube with a diameter of ≥14 (e.g., 1–2 capsule contents mixed well in 10 mL applesauce followed by water flush).
  • If dose requires more than two capsules, repeat above until prescribed dose is reached.
* Dose lipase units per Table 7 instructions.

Table 9B. Three Pancreatic Enzyme Delivery Options for EN*

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Method 3: Other Reported Procedures for Delivery of Oral Pancreatic Enzymes for Enteral Nutrition (NOT FDA-Approved)*
Give by tube Mixed with Food Mixed with Thick Liquid Mixed with Liquid Comments and Tips
Enteric-coated formulations Creon, Pancreaze, Zenpep While FDA approval exists for Pertzye microspheres, clinical experience exists for other enteric-coated beads, microtablets, spheres and and microspheres utilized in other products
Tube Size 16–18 Fr 10+ Fr† 10+ Fr† 1. Larger tubes have lower clog risk
2. Liquid mixtures (e.g., bicarbonate mixture) may have fewer clogging issues with small tube sizes vs. delivery of PERT with food or thickened liquid
Example Applesauce Nectar-thick liquid Bicarbonate mixture (Table 11) The exact food/liquid is less important than the consistency of the mixture and a pH <4–4.5
Volume Food/Liquid per Capsule 15 mL 50–100 mL 40–65 mL of bicarbonate mixture
Mixing Stir and administer immediately Stir gently to suspend capsule contents in thickened liquid Crush capsule contents and mix, before use 1. Crushing enteric- coated products may increase risk of enzyme deactivation
2. Alternative with bicarbonate-containing solutions: consider gradually dissolving over 20–30 minutes
Prep Stop EN and flush tube prior to administering PERT Flushing with water BEFORE administration prevents activation of enzyme in the tube which causes clogging
Administration Administer mix with slow, gentle pressure
Flush Flush tube, resume EN Flushing with at least water BEFORE and AFTER administering prevents clogging.
Give by mouth Comments and Tips
Enteric-coated formulations Creon, Pancreaze, Pertzye, Zenpep Do not chew capsules
Nonenteric-coated formulations Viokace While crushed Viokace can be mixed with EN, caution must be taken to avoid inhalation injuries and contact skin irritation
If Viokace given by mouth, patient will need acid suppression
Administration Administer by mouth every 3–4 hours during EN infusion For nocturnal feeding, some patients prefer to take PERT before bed, once during the night, and once in AM before infusion ends
* Dose lipase units per Table 7 instructions.
† If using 10 to 12 Fr feeding tubes, low-dose enzyme capsules (3,000 to 5,000 units of lipase) are recommended as they contain the smallest sized capsule contents to avoid tube clogging.

Table 10. Pancreatic Enzyme Delivery for EN – Advantages and Limitations

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Product Advantages Limitations
Lipase cartridge
  • FDA approved for EN use
  • Research shows efficacy with EN
  • Maintains closed EN systems
  • Ease of use
  • Does not contribute to total daily lipase limit
  • Continuously hydrolyzes fat in the formula during EN infusion
  • Requires pump for EN infusion
  • Cannot use with oral diet
  • Cannot use with bolus or gravity feeding
  • Cannot use formulas with insoluble fiber as they clog the cartridge
  • Availability dependent on individual hospital or outpatient pharmacy
  • Requires new cartridge for every 500 mL of formula needed
  • Formulas vary in % fat hydrolysis https://www.relizorb.com/docs/pdfs/Compatible-Formulas-and-Pumps.pdf
Oral/enteral pancreatic enzymes
  • Can be used for bolus feedings
  • Does not require a pump
  • Can be given orally or with EN
  • Broad availability in hospital or outpatient pharmacies
  • Only one product FDA-approved for EN use
  • Lacks research showing efficacy with EN despite historical use
  • Counts toward total daily lipase units
  • Crushing enzymes is labor intensive
  • Using crushed enzymes increases the chance of clogging a feeding tube
  • If given orally, must be given frequently since enzyme activity is time-limited
  • Enzymes and EN may not mix effectively if not delivered together

Table 11. Sodium Bicarbonate Sources for Mixing with Pancreatic Enzymes

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Source mEq bicarb and sodium
Sodium bicarbonate solution
  • 8.4% solution (84 mg/mL)
  • 650 mg tablet dissolved in 65 mL of water
  • 325 mg tablet in 40 mL water
  • 1 mEq/mL each of bicarbonate & Na
Sodium bicarbonate powder (same as baking soda)
  • 500 mg
  • 650 mg
  • 6.2 mEq each of bicarbonate and Na
  • 7.7 mEq each of bicarbonate and Na
Baking soda (from your kitchen)
  • 1/8 teaspoon
  • 6.7 mEq each of bicarbonate and Na
Notes:

• For each 10,000 units of lipase, 10 mL of 8.4% sodium bicarbonate is recommended.

• Monitor basic metabolic panel for serum bicarbonate level to ensure patient does not become alkalotic on sodium bicarbonate dose.

• Do not use calcium carbonate or magnesium aluminum hydroxide antacids as both have been shown to reverse the beneficial effects of enzyme therapy by causing precipitation of calcium and magnesium soaps.

Table 12. Factors That Affect Oral Pancreatic Enzyme Efficacy

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  • Enzymes are dosed inadequately.
  • Enzyme is outdated.
  • Delayed gastric emptying causes poor mixing of enzymes with food and prolonged exposure to gastric acid.
  • Rapid small bowel transit reduces mucosal contact time.
  • Timing of enzymes is inappropriate such as taking at completion of meal instead of at beginning/during meal.
  • Gastric and intestinal environment is too acidic. The optimal pH for enzyme activation is >5.5 (lipase is irreversibly inactivated at pH of <4). Therefore, an acid-suppressing agent may be needed.
  • Enzymes are improperly stored (exposed to heat—e.g., in the car, in a clothing pocket) or taken with hot drinks, which can denature enzymes.
  • Over-the-counter generic enzymes are used and are not bioequivalent to prescription enzymes.
  • Enzyme capsule contents are chewed or crushed.
  • Delayed dissolution of enteric-coated enzyme capsule contents in the small bowel shifts absorption sites distally.
  • Capsule contents have prolonged exposure to alkaline foods or fluids.
  • Patient does not take enzymes as prescribed.
Notes:

• All PERT work optimally in pH >5.5. Proton pump inhibitors produce 90% reduction in acid secretion vs. only 50% with H2 receptor antagonists.

PERT activity peaks about 30 minutes after ingestion and last about 2 hours.

Measuring Responses to Treatment of Malabsorption

Measuring Responses to Treatment of Malabsorption

  • Monitor the patient for a reversal of the signs and symptoms that caused the clinician to consider fat malabsorption in the patient:

Signs that patients are responding to therapy

  • Nutrition:
    • Weight goals are achieved.
    • Refeeding syndrome may appear if the patient is now able to absorb nutrients.
    • Fat-soluble vitamin deficiencies are improved or resolved (if fat-soluble vitamins were provided in adequate amounts).
      • Serum vitamin A and vitamin D are negative acute phase reactants and should not be drawn in the setting of inflammatory process or infection.
    • Hyperglycemia presents itself now that EN absorption is improved in patient with diabetes. Unrecognized diabetes may become apparent and patients with a history of diabetes may require escalation of their diabetes regimen.
  • Gastrointestinal:
    • GI symptoms are improved or resolved: diarrhea, gas, bloating, cramping, abdominal distension, fecal urgency, foul smelling stools, steatorrhea, etc.

Considerations if patients are not responding to therapy

  • Failure to gain weight
    • Enteral formula considerations
      • Is the patient actually receiving the prescribed enteral volume (calories)?
      • Is the enteral calorie prescription adequate for the patient?
      • Is the patient adequately hydrated?
      • Is good glycemic control achieved?
      • Should type or delivery of PERT be altered?
      • Is PERT supplementation adequate?
      • Does the patient need acid suppression to maximize PERT therapy?
      • Is the patient compliant with all therapies?
  • No resolution to GI symptoms
    • Recheck fecal fat excretion
    • Reconsider initial diagnosis and evaluate other potential causes of GI symptoms

Recommendation Grading

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