Overview and Prevalence

Diagnosing Fat Malabsorption

Enteral Nutrition Options in the Patient with Fat Malabsorption

Measuring Responses to Treatment of Malabsorption

Design and created by Guideline Central in participation with the Consensus and Physician Experts.

Optimizing Enteral Nutrition Support for Adult Patients with Fat Malabsorption

Consensus and Physician Experts

Publication Date: September 18, 2020

Table 2. Potential Causes of Fat Malabsorption

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.

Table 3. Tests for Fat Malabsorption

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.

Table 5. Vitamin Deficiencies Associated with Fat Malabsorption

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

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

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

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).

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

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.

Table 9A. Three Pancreatic Enzyme Delivery Options for EN

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*

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

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

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.

Disclaimer

This resource is for informational purposes only, intended as a quick-reference tool based on the cited source guideline(s), and should not be used as a substitute for the independent professional judgment of healthcare providers. Practice guidelines are unable to account for every individual variation among patients or take the place of clinician judgment, and the ultimate decision concerning the propriety of any course of conduct must be made by healthcare providers after consideration of each individual patient situation. Guideline Central does not endorse any specific guideline(s) or guideline recommendations and has not independently verified the accuracy hereof. Any use of this resource or any other Guideline Central resources is strictly voluntary.

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).

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

Optimizing Enteral Nutrition Support for Adult Patients with Fat Malabsorption

Overview and Prevalence

Key Point

Prevalence of Target Diseases

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