DOI: 10.1002/ncp.

10960

INVITED REVIEW

Enteral nutrition product formulations: A review

of available products and indications for use

April Church MS, RD1 | Steph Zoeller RD2

1
Nutrition Services, Asante Rogue
Regional Medical Center, Medford,
Oregon, USA
2
Orlando VA Healthcare System,
Orlando, Florida, USA
Correspondence
April Church, MS, RD, Nutrition Services,
Asante Rogue Regional Medical Center,
2825 E. Barnett Rd, Medford, OR 97504,
USA.
Email: april.church@asante.org
Abstract
When oral nutrition is not feasible, enteral nutrition (EN) therapy is often
considered the preferred route of nutrition support to meet the nutrient needs
of individuals with a functional gastrointestinal tract across multiple levels of
care (critical care, acute care, and home care). Enteral formulations have
progressively evolved over the last 50 years from the simple blending of
hospital food thin enough to run through a feeding tube, to the development of
commercial standard formulas, followed by specialized formulas with
immune‐modulating and disease‐specific qualities, to the most recent shift
to food‐based or blenderized EN composed of natural, whole foods with
perceived health benefits. With the vast number of enteral formulations on the
market, clinicians may be overwhelmed trying to determine proven vs
theoretical benefits. This review is intended to explore differences in enteral
formulations, identify implications for clinical practice, and review evidenced‐
based clinical guidelines to assist clinicians in enteral formula selection.

KEYWORDS
adults, enteral formulas, enteral nutrition, nutrition support

I N T R O D U C TI O N contamination and ease of administration.3 Recently in

Enteral nutrition (EN) is defined as a “system of providing
nutrition directly into the gastrointestinal (GI) tract via a
tube, catheter, or stoma that bypasses the oral cavity.”1 EN
helps to maintain gut integrity by maintaining normal
digestion and absorption, prevents bacterial adherence
and translocation, and provides structural support for the
mucosa, maintaining immune function.2(227–249) EN for-
mulations have come full circle in the last 50 years. Prior
to 1973 when the first nutrient‐intact formula came on the
market, EN consisted of blenderized foods blended thin
enough to be provided through a feeding tube.3 The use of
commercial enteral formulas became standard of practice
in hospitals because of the decreased risk of microbial
the last 10 years there has been a consumer shift with
trends in food selection and consumption to whole food,
organically grown, locally sourced, functional foods with
perceived health benefits. The health‐conscious trend has
translated over to the EN world primarily in pediatrics
and home EN (HEN) patients with a desire to prepare
home‐made blends with more holistic foods. To meet the
demands of consumers, manufacturers began marketing
commercially prepared food‐based blenderized enteral
formulations in addition to their current commercial
product lines. With the addition of food‐based blenderized
EN, there are now a vast number of enteral formula
options present on the market, which include standard
(polymeric), semielemental, disease‐specific, and specialty

© 2023 American Society for Parenteral and Enteral Nutrition.

Nutr. Clin. Pract. 2023;38:277–300. wileyonlinelibrary.com/journal/ncp | 277


278 | CHURCH and ZOELLER
formulations with phytonutrients and proposed pharma-
cological properties.
Disease‐specific and specialty formulas often lack
evidence from high‐quality clinical trials to validate the
formula claims. The US Food and Drug Administration
(FDA) classifies EN as a “medical food,” which translates
to “a food which is formulated to be consumed or
administered enterally under the supervision of a
physician and which is intended for the specific dietary
management of a disease or condition for which
distinctive nutrition requirements, based on recognized
scientific principles, are established by medical evalua-
tion.”3,4 The FDA does not consider medical foods as
drugs, therefore, the FDA does not subject companies
marketing EN formulas to any regulatory requirements
that specifically apply to drugs.3,4 Medical foods are
exempt from labeling requirements including both
nutrient content and health claims.3,4 Clinical trials are
not required to determine safety and efficaciousness of
enteral formulas prior to manufacturing, marketing, and
distribution.3,4
Clinicians are charged with the task to prescribe the
EN formula best suited to meet the nutrient needs
and metabolic demands of the patients. Clinicians also
attempt to choose a formula that synchronizes the overall
clinical picture with patient lifestyle preferences, “right
formula for the right patient.” With enteral formulations
flourishing in the market, clinicians are tasked with
sifting through the literature and evaluating clinical trial
results to determine if specialty formulas can corroborate
their claims. This review aimed to evaluate current
enteral formulations and assist clinicians in making the
appropriate selection for their patients by reviewing
clinical trials, systematic reviews, and consensus or
clinical guidelines from respected societies published
within the last 10 years.
REVIEW OF EN FORMULATIONS
Enteral formulas can be classified into two major
categories: standard (polymeric) and chemically defined
(semielemental/elemental). These two categories can be
further divided into additional subcategories including
disease‐specific and specialty (immune‐enhancing).
Another emerging class of EN formulations includes
food‐based blenderized EN and is usually divided into two
primary categories: commercially prepared food‐based EN
and home‐prepared or blenderized EN. Commercially
prepared food‐based EN can be further categorized into
standard (polymeric), semielemental, disease‐specific, and
immune‐enhancing and may or may not be plant‐based.
Each category is variable in terms of composition and
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concentration, providing differing levels of macronutrient,
micronutrient, and fluid content and in some cases
additional pharmacologically active substances.5
Standard polymeric formulas
Standard polymeric formulas are nutritionally complete
in terms of macronutrients and micronutrients meeting
dietary reference intakes within a specified volume,
typically 1000–1500 ml. These formulas are designed to
meet the nutrient needs of healthy individuals but also
have become the standard practice in nutrition support
for hospitalized patients both in acute and critically
illness, as well as patients receiving long‐term EN at
home. Standard polymeric formulas come in variable
concentrations from 1 to 2 cal/ml. Carbohydrates serve as
the primary energy source consisting of oligosaccharides
(3–10 glucose units) or polysaccharides (>10 glucose
unites) usually in the form of corn syrup solids or
maltodextrin. Carbohydrates make up about 40%–70% of
the macronutrient energy composition for most formu-
las. Most standard polymeric formulations are suitable
for individuals with lactose intolerance. Standard poly-
meric formulas contain intact proteins primarily in the
form of casein or soy isolates but may also include whey
protein concentrate, lactalbumin, milk protein concen-
trate, and sodium, calcium, magnesium, and potassium
caseinates. Proteins make up approximately 15%–20% of
the macronutrient composition in standard formulations.
Standard formulations require individuals to have
normal levels of pancreatic enzymes for digestion and
absorption due to the intact‐protein content.2(227–249) The
third macronutrient component, fats, serve as a valuable
source of energy, typically 15%–30% of total formula
calories and provides the essential fatty acids (linoleic
and linolenic acids). Fats are included as triglycerides
with a combination of long‐chain triglycerides (LCT) and
medium‐chain triglycerides (MCT) and/or structured fats
primarily consisting of ω‐3 fatty acids (alpha‐linolenic
acid [ALA], eicosapentaenoic acid [EPA], and docosa-
hexaenoic acid [DHA]), which are believed to have anti‐
inflammatory and immune‐enhancing effects.2
Fat sources include primarily corn and canola oil, but
may also include coconut oil, fish oil, high‐oleic sun-
flower oil, MCT, palm kernel oil, safflower oil, soybean
oil, soy lecithin, monoglycerides and diglycerides. Stan-
dard enteral formulas are 70%–85% water by volume,
dependent upon the energy density of the formula.
Additional free water provided in addition to enteral
feeds may be required to meet the hydration needs of the
patient and prevent tube occlusion.2 Standard formula-
tions may or may not include fiber.

NUTRITION IN CLINICAL PRACTICE
Standard formulations are recommended as the first
line of practice in critical care, acute care, and patients
receiving HEN.2 The 2022 European Society for Clinical
Nutrition and Metabolism (ESPEN) guidelines for patients
receiving HEN recommend the use of standard commer-
cial formulas for patients without diarrhea, constipation,
or diabetes unless there is a specific justification for
the use of blended tube feed.6 The 2016 American Society
for Parenteral and Enteral Nutrition (ASPEN)/Society
of Critical Care Medicine (SCCM) clinical guidelines for
nutrition support in adult patients who are critically ill
recommend use of standard polymeric formulas (isotonic
or near isotonic 1–1.5 cal/ml) with initiation of EN in the
intensive care unit (ICU).7 Routine use of specialty
formulas in patients who are critically ill in the medical
ICU (MICU) and disease‐specific formulas in the surgical
ICU (SICU) are not recommended.7 The rationale for the
use of standard formulas in the critically ill is due to lack
of clinical evidence showing benefit with use of disease‐
specific or specialty formulas over standard formulations.7
Concentrated formulas
Concentrated formulas are nutrient‐dense standard
formulas, 1.5–2 cal/ml, which require normal digestion.
Volume‐restricted formulas are indicated for hypervo-
lemic hyponatremia, renal or heart failure, syndrome of
inappropriate antidiuretic hormone, fluid retention,
ascites, and reduced urine output.3 Concentrated
formulas may also be beneficial in patients with
increased caloric or nutrient requirements and toler-
ance to smaller feeding volumes related to the adminis-
tration method via enteral access device (EAD) as in
cyclic and bolus feeding.5 Concentrated formulas may
also be preferential in patients receiving HEN who may
desire liberalization from prolonged feeding times
(cyclic) or decreased feeding frequencies (bolus and
intermittent regimens) as nutrition goals can be met in
decreased volumes. It is important for clinicians to note
when prescribing concentrated formulas for patients not
on restricted fluids, additional free water flushes may
need to be administered to meet individual hydration
requirements. Clinicians should also pay close attention
to the volume required to meet 100% of the daily
reference intakes and micronutrient needs of the
patients who may require long‐term EN to ensure
deficiencies do not occur. 2016 ASPEN/SCCM guide-
lines state that “Disease specific and severe fluid‐
restricted formulas may be rarely used in a small
percentage of patients on a case‐by‐case basis due more
to physiologic benefits, such as electrolyte profile
and volume restriction (renal).”7 The guidelines further
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| 279
state that volume‐restricted nutrient‐dense formulas
(1.5–2 kcal/ml) may be considered for patients with
acute respiratory failure in a state of volume overload.7
Elemental/semielemental formulas
Elemental and semielemental formulations contain
partially or completely hydrolyzed nutrients with the
intended purpose to maximize nutrient absorption.2 Due
to the structural form of elemental and semielemental
formulas minimal digestion is required.2 Peptide formu-
las may be beneficial for patients with persistent
diarrhea, pancreatic disorders, and other malabsorptive
conditions.8 Carbohydrate sources include hydrolyzed
corn starch, fructose, or maltodextrin. Protein presents in
the form of hydrolyzed proteins—dipeptides, tripeptides,
and free amino acids—which are readily absorbed by the
intestine and require no further hydrolyzation. Protein
sources include hydrolyzed casein, hydrolyzed whey, soy
protein isolate, or crystalline L‐amino acids. Altered fats
present primarily as medium‐chain triglycerides (MCT)
with sources including fatty acid esters, fish oil, palm
oil, coconut oil, safflower oil, sardine oil, soybean oil,
soy lecithin, and structured fats (ω‐3 fatty acids). MCT
are absorbed directly into small intestine mucosa and are
transported to the liver following absorption via the
portal vein. MCT also do not require lipase or bile salts
for digestion and absorption.2 Due to increased amount
of MCT, elemental and semielemental formulas may
be low in or contain zero essential fats and patients
may be at risk for essential fatty acid deficiency with
long‐term use.2
There is limited research to analyze the efficacy of
semielemental formulas and cost vs benefit outcomes
when compared with standard formulations. Qiu et al9
conducted a multicenter, single‐annonymized, ran-
domized controlled trial of 144 ICU patients requiring
EN for minimum of 5 days. Patients received a fat‐
modified enteral formula containing MCT, carnitine,
and taurine (interventional feed group) or standard
formula. Feeding tolerance was assessed by evaluating
diarrhea, vomiting, gastric retention, and abdominal
distension.9 Caloric and protein provision was signifi-
cantly greater in the intervention feed group
(P < 0.01).9 Total incidence of feeding intolerance
was significantly lower in the interventional feed
group (42.3%) vs control group (65.7%) (P < 0.001).
There were no statistically significant differences in
mechanical ventilator–free days, length of stay (LOS),
and in‐hospital mortality.9 Seres et al10 conducted a
randomized pilot study to evaluate efficacy, tolerance
and safety of a peptide‐based high‐protein, high–ω‐3

280 | CHURCH and ZOELLER
fat enteral formula vs a high‐protein standard formula
in 49 patients who were critically ill in the MICU,
SICU, and cardiothoracic ICU. Characteristics of the
peptide‐based formula include 1.2 cal/ml, 75 g/L pro-
tein with protein sources from hydrolyzed whey
protein/hydrolyzed sodium caseinate, 110.6 g carbohy-
drate/L with source maltodextrin, 53.9 g/L fat with
MCT/fish oil/canola oil/soy oil; MCT:LCT ratio of 45:5,
and fiber source from short‐chain fructooligosaccar-
ides (FOS). The high‐protein standard formula was
also 1.2 cal/ml; but the macronutrient composition
included 55.5 g/L protein with protein sources sodium
and calcium caseinate, 157.5 g/L carbohydrate with
source maltodextrin, 39.3 g/L fat with high‐oleic
safflower oil, canola oil, MCT, soy lecithin with
MCT:LCT ratio of 20:80, and contained no fiber. Daily
measures of GI complications were obtained including
diarrhea, constipation, nausea, vomiting, high gastric
residuals, ileus, distention, abdominal pain, colonic
dilation, GI bleed, upset stomach, abdominal tender-
ness, and GI discomfort. Data on metabolic abnormal-
ities, infections, mortality, ventilator duration, and
LOS were also collected daily. Mean daily intakes were
similar between the two groups (P = 0.6). The study
found there was a significant reduction in the number
of days with adverse events (4.33 vs 9.92, P = 0.03) and
a significant reduction in GI complications (4.29 vs
7.13, P = 0.0489, [odds ratio] OR = 2.79) in the peptide‐
based, high‐protein, high–ω‐3 formula compared with
standard formula. The authors acknowledged that, due
to the small sample size in this pilot study, more larger
randomized controlled trials are needed to confirm the
outcomes and benefits of this study.10
Elemental and semielemental formulas are marketed
for use in patients with GI disorders, malabsorptive
conditions, or have failed tolerance with standard
polymeric formulas. Limited data are available substan-
tiating free amino acid and peptide‐based formulas over
standard formulas in patients with malabsorptive condi-
tions. Consequently, the 2016 ASPEN/SCCM clinical
guidelines state “we suggest considering use of small
peptide enteral formulas in patients experiencing persist-
ent diarrhea, with suspected malabsorption or lack of
response to fiber”7 with a low quality of evidence due to
sparsity of large prospective clinical trials.7
In patients with GI disorders, EN is often indicated
as part of the treatment plan.7,11–13 Some of the GI
disorders that may benefit from EN includes inflammatory
bowel disease (IBD), Crohn's disease (CD), and
pancreatitis.7,11–13 ESPEN published evidenced‐based
guidelines in 2020 summarizing clinical nutrition recom-
mendations in acute and chronic pancreatitis (CP).
ESPEN recommends standard formulas as the first line
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of therapy in acute pancreatitis.11 This recommendation is
in accordance with the 2016 ASPEN/SCCM guidelines to
prescribe a standard polymeric formula with EN initiation
in severe acute pancreatitis.7,11 In the presence of EN
intolerance in severe acute pancreatitis, ASPEN/SCCM
2016 suggests “changing from a standard polymeric
formula to one that contains small peptides and MCTs
or to one that is nearly fat‐free elemental formulation.”7 A
semielemental formula may be of benefit in patients with
severe acute pancreatitis that may be experiencing
malabsorption per ESPEN guidelines.11 For patients with
chronic pancreatitis intolerant to standard formulas,
ESPEN recommends the use of semielemental formulas
with MCT.11 ESPEN notes that there is limited evidence
available to evaluate the ideal composition for EN,
but that semielemental formulas have shown good
tolerance.11 ESPEN also recommends patients with CP
experiencing pancreatic exocrine insufficiency or signs of
exocrine failure without symptom improvement on a
semielemental formula, suggest administering pancreatic
enzymes with the enteral formula. This recommendation
may not be supported by other societies and may go
against the manufacturer guidelines for administration.
Formula selection for patients with CP or cystic fibrosis
undergoing pancreatic enzyme replacement therapy
is dependent upon the type of therapy the patient is
undergoing.14 If pancreatic enzyme replacement is via an
external enzyme filtration device, clinicians should be
apprised of the enteral formulations that are compatible
(certain polymeric and semielemental/elemental formu-
las) and incompatible with the device such as formulas
containing insoluble fiber and food particulates.14
ESPEN also published practice guidelines summariz-
ing clinical nutrition recommendations in IBD (2020)
and chronic intestinal failure (2021). The guidelines
recommend in patients with active IBD/CD a standard
polymeric formula with moderate fat content be used as
primary and supplemental therapy.12 Clinical trials failed
to show any significant difference between elemental,
semielemental, oligomeric and polymeric diets.12 Elemen-
tal and polymeric formulas show no significant difference
in remission rates for CD.12 For patients with short bowel
syndrome where EN is indicated, studies found that
elemental and standard formulas showed similar levels of
nutrient absorption and fluid and electrolyte losses.13
ESPEN recommends polymeric isotonic enteral diets for
short bowel syndrome due to the lower cost and decreased
osmolarity of the standard formula over elemental
formulas.13 Due to limited availability of clinical trials to
support the efficacy of elemental and semielemental
formulas, use of an elemental formula may be reserved
for patients with malabsorption who have failed trials with
standard formula.

NUTRITION IN CLINICAL PRACTICE
Fiber‐supplemented formulas
Enteral formulations containing fiber may support
normal digestive health. Classifications of fiber are
based on structure, fermentation potential, viscosity,
and solubility.15 Dietary fiber is commonly classified by
its water solubility, which includes the two categories
soluble and insoluble fiber. Fibers are the portion of
plant‐derived food that cannot be completely broken
down by the human digestive system. EN formulations
containing fiber may be composed of a single source or
blend of fibers in variable proportions.15 Common
sources of fiber in EN formulations include guar gum,
soy polysaccharide, pea fiber, oat fiber, oligosacchar-
ides, inulin, FOSs, lignin, Arabic gum, and soy fiber.
Fiber type and amount may impact the physiological
effects in the GI tract.15 The importance of soluble fiber
is related to its role in short‐chain fatty acid (SCFA)
production. Soluble fiber feed the bacteria and micro-
biota of the large intestine which are metabolized into
SCFAs that act as an energy source for colonocytes and
promotes the absorption of water and electrolytes.2,5,16
SCFAs may have the capability to aid in maintenance of
the intestinal gut barrier and prevent bacterial trans-
location.15 Soluble fiber also aids in gastric emptying by
retaining water as it moves through the digestive
system.2,16 The uptake of water and electrolytes may
also provide an antidiarrheal effect.15 Insoluble fiber
may assist with preventing or alleviating constipation
with its bulking effect in the large intestine. Insoluble
fiber does not dissolve in water, is unaffected by
digestive enzymes, and triggers secretion of mucus in
the large intestine which provides a bulking effect
increasing stool weight and increasing stool transit time
throughout the GI tract.5,8,16 Fiber‐containing formulas
are considered for the management of both diarrhea and
constipation due to the proposed functionality of fiber to
maintain GI motility and regularity.5,8,16
Most of the clinical trials with regards to EN and fiber
focus on diarrhea. Yagmurdur et al17 conducted random-
ized controlled study with 120 patients with acute
cardiovascular disease aged 35–90 years old, on mechan-
ical ventilation requiring EN via nasogastric tube.
The control group received a fiber‐free formula, and
the study group received a fiber‐enriched formula
(soluble/insoluble fiber 1:1 ratio, 0.7 g and 0.8 g per
100 ml, respectively). The fiber content of the fiber‐
enriched formula consisted of 32% soy polysaccharides,
24% Arabic gum, 12.5% inulin, 12% alpha‐cellulose,
10.5% oligofructose, and 9% resistant starch.17 The most
common GI complication in the study was diarrhea.17
The fiber‐enriched formula group had statistically
significantly less diarrhea (P < 0.001).17 There were no
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| 281
statistical differences observed between the two study
groups with regards for other GI complications (vomit-
ing, regurgitation, distention, and constipation) and no
significant differences in any of the biochemical parame-
ters measured.17 Zaman et al18 conducted a systematic
review and meta‐analysis of prospective studies to
evaluate the effect of dietary fiber and prebiotic
supplementation in enteral formulas on diarrhea, fecal
microbiota, and SCFAs. For the review, 22 experimental
studies and 4 observational cohort studies met inclusion
criteria. Soy polysaccharide was the most extensively
investigated fiber in EN (7 studies) followed by
mixed fiber (6 studies); partially hydrolyzed guar
gum (3 studies), psyllium (3 studies); oat and soy fiber
(2 studies), FOS (1 study), inulin (1 study), banana flakes
(1 study), glactomannan (1 study), and a final study did
not mention fiber type.18 Fiber dosage ranged from 5.2 to
39.0 g/day.18 The results of the meta‐analysis of 14
experimental studies with data on diarrhea incidence
during EN (fiber‐containing EN vs fiber‐free EN) showed
that fiber reduced diarrhea in patients receiving EN
(OR = 0.47; 95% CI, 0.29–0.77; P = 0.02).18 The study
reported the main limitation of the review was heteroge-
neity of the patients including critical illness and
noncritical illness, use of antibiotics, and each study's
definition of diarrhea. Studies were excluded from the
meta‐analysis if the diarrhea definition did not indicate a
measurable outcome. Overall, the systematic review
demonstrated that fiber assists to minimize diarrhea in
adult patients undergoing fiber‐enriched EN.18
Cara et al19 completed a systematic review and meta‐
analysis of 19 studies evaluating the safety, potential
adverse events, and health outcomes of using fiber‐
containing EN formulations in adult patients who were
critically ill. Fiber content included soluble fiber (13
studies), mixed fiber with soluble/insoluble (4 studies),
insoluble fiber (1 case report), and unspecified (1 case
series). Random‐effects meta‐analysis models showed
diarrhea scores were significantly lower in the fiber
groups compared with nonfiber groups (pooled mean
difference, −2.78; 95% CI, −4.10 to −1.47).19 Models from
three randomized controlled trials with 265 total
participants showed that fiber groups had a 39% lower
risk of GI complications overall (abdominal distention,
bowel obstruction, constipation, flatulence/gas, gastric
residuals, nausea/vomiting, and/or regurgitation/aspira-
tion) when compared with nonfiber groups (pooled risk
ratio [RR], 0.61; 95% CI, 0.47−0.79). No group differences
were noted in individual GI complications, mortality,
and ICU or hospital LOS. Stratified analysis of soluble or
mixed fiber interventions reduced heterogeneity in the
models but resulted in identical conclusions. The study
concluded that EN formulas containing fiber may have

282 | CHURCH and ZOELLER
no effect on adverse events in patients with critical illness
when compared with nonfiber formulations. EN formu-
las containing fiber or fiber supplementation may reduce
incidence and severity of diarrhea and GI complications
overall in patients who are critically ill. The study noted
limitations including lack of consistent outcome
measurements and reporting across the studies for GI
complications and method for measuring diarrhea. Only
six studies used the same method for diarrhea which
these differences in measure outcomes decreased the
number of studies that could be included in the analysis
for the relevant results.19
Fu et al20 conducted a retrospective study with a
prospective cohort of 129 adult patients ≥18 years old in the
ICU to determine if fiber could be safely tolerated in the
adult population who were critically ill and the relationship
between dietary fiber intake and SCFA production within
the GI microbiome. The primary outcomes to be measured
included the relative abundance (RA) of SCFA producers
based on 16S ribosomal ribonucleic acid (RNA) gene‐
sequencing results and fiber tolerance in patients who were
critically ill. Rectal swabs were taken at ICU admission and
72 hours (h) later. Nutrition intakes were calculated and
recorded for patients who received nothing by mouth, EN,
or an oral diet. The amount of soluble fiber in each type of
feed was obtained and total fiber intake calculated over
72 h. The median fiber intake during the 72 h after ICU
admission was 13.4 g/day (0–35.4 g/day) with less acutely ill
patients receiving more fiber.20 No difference in GI events
(bowel obstruction, nausea or vomiting, enteric infections,
edema, or diarrhea) based on fiber intakes was noted.20
Patients with high fiber intake were less likely to have
abdominal distention (11% high fiber vs 28% in no fiber
group, P < 0.01) and no difference in diarrhea incidence
(15% in high fiber vs 13% in no fiber group, P = 0.94).20 The
high fiber intake group had higher RA of SCFA producers
after 72 h compared with low‐fiber groups.20 After correct-
ing for energy intakes, the median RA of SCFA producers
after 72 h was 0.41%, 0.32%, and 2.35% in the no, low, and
high corrected fiber categories (P < 0.01).20 High fiber
intakes were associated with higher fecal microbial
diversity (P = 0.04).20 The study concluded that higher
fiber intakes were associated with higher levels of SCFA‐
producing bacteria which may promote the growth of
beneficial gut microorganisms in patients who were
critically ill whose microbiome homeostasis may be
disrupted. Fiber intake was not associated with adverse
GI events in patients who were critically ill. Limitations of
the study included fiber intakes were heterogenous and the
effect of fiber‐specific properties could not be measured.20
Inconclusive recommendations with regards to rou-
tine use of fiber‐containing formulas in clinical practice
remains. The 2016 ASPEN/SCCM guidelines suggest “a
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mixed fiber formula should not be routinely used in the
adult critically ill patient prophylactically to promote
regularity or prevent diarrhea.”7 Use of a commercial
soluble/insoluble containing formula may be considered
in the presence of persistent diarrhea.7 Both soluble and
insoluble fiber should be avoided in patients with an
increased risk for bowel ischemia or severe dysmotility.7
Conversely, the 2015 Canadian Clinical Guidelines
Practice Committee suggest that there are “insufficient
data to support the routine use of fiber (soluble or
insoluble) in enteral feeding formulas in critically ill
patients.”21
Patient population and clinical setting may determine
a clinician's decision whether to prescribe a EN formula
containing fiber.5 Amount and fiber composition should
be considered when making the decision to prescribe an
EN formula in patients with either constipation or
diarrhea. It may be beneficial to provide fiber in a
medically stable hospitalized patient or long‐term HEN
patient, but one must use caution with the use of fiber in
the critical care setting or hypotensive patients at risk for
bowel ischemia or bowel obstruction.
Disease‐specific formulas
Diabetes mellitus formulas
Diabetic formulas are marketed for use in patients with
diabetes and designed to theoretically improve glycemic
control and reduce insulin requirements.22,23 The for-
mula design is lower in carbohydrate content (35%–40%
of total calories) with a low‐glycemic index and higher fat
(40%–50% of total calories) with a higher percentage of
monounsaturated fatty acids.23–25 Protein content may or
may not be higher than standard formula. Fiber is also
increased with a blend of soluble, insoluble fiber and
prebiotics over standard enteral formulations.23,24
A randomized, controlled, double‐annonymized, cross-
over study conducted by Lansink et al22 in 23 ambulant
nonhospitalized participants with type 2 diabetes for
>6 months compared participants receiving a diabetes‐
specific high‐energy, high‐protein, low‐carbohydrate for-
mula containing a low‐glycemic index carbohydrate to an
isocaloric, fiber‐containing standard formula. Participants
received EN via nasogastric feeding tube for 4 h after an
overnight fast of 10 h. To meet eligibility criteria the
participants had to be on a controlled antihyperglycemic
regimen with metformin and/or sulfonylureas for at least 2
months and expected to continue on current regimen
throughout the duration of the study. Composition of the
diabetes‐specific formula included 1.5 cal/ml formula, 31%
of energy derived from carbohydrate with no added

NUTRITION IN CLINICAL PRACTICE
fructose, 20.5% of energy derived from protein; and
enriched with six different dietary fibers. The fibers
included a combination of soluble, insoluble, fermentable,
and nonfermentable fibers (15 g/L of formula with an 80%
soluble and 20% insoluble fiber ratio). The standard
formula's characteristics included 1.53 cal/ml formula,
47.9% of energy derived from carbohydrate, 15.7% of energy
derived from protein; and enriched with the same
fiber combination as the diabetes‐specific formula. The
glucose profile results from 0 to 4 h for the diabetes‐
specific formula group vs the standard formula group
reported in mean ± SD was as follows: for peak
glucose concentration, 8.3 ± 1.1 vs 10.1 ± 1.7 mmol/L,
and for mean glucose concentration 7.4 ± 1.0 vs
8.4 ± 1.3 mmol/L.22 The insulin profile results from 0 to
4 h for the diabetes‐specific formula group vs the standard
formula group for peak insulin concentration 44.9 ± 34.6
vs 60.6 ± 45.3 pmol/L; mean insulin concentration
32.1 ± 28.4 vs 44.3 ± 36.3 pmol/L.22 The results showed a
lower mean delta‐glucose concentration in the diabetic
formula group in the 3‐ to 4‐h period (0.3 ± 1.0 and
2.4 ± 1.5 mmol/L; P < 0.001); and delta‐peak concentra-
tions, delta‐mean concentrations, and incremental area
under curve for glucose and insulin were significantly
lower with diabetes‐specific formula compared with
standard formula (all comparisons P < 0.001).22 The
results showed administration of a high‐energy, high‐
protein, low‐carbohydrate diabetes‐specific formula im-
proved glucose profiles, lower glucose levels, and lower
insulin requirements with no significant differences in
tolerance when compared with a standard formula.
Limitations recognized by the study included short
feeding period of 4 h and insulin was not used for blood
glucose control, making it difficult to translate the results
into clinical practice for patients treated with insulin.22
Evidence demonstrating benefits of a diabetes‐specific
enteral formula to improve glycemic control is limited. In
a randomized controlled open‐label study with 101
patients with critical illness >18 years old, requiring an
ICU stay for >48 h in need of EN support were
administered either a low‐carbohydrate formula or a
standard fiber formula.26 The low‐carbohydrate formula
and standard formula were comparable in calories
(1.5 cal/ml) but differed in macronutrient composition.26
The low‐carbohydrate formula contained 127.5 g/L carbo-
hydrate and 75 g/L fat and the standard formula contained
188 g/L carbohydrate and 58 g/L fat. The standard formula
group received an enteral protein supplement to equate
the protein content of the formulas. The study participants
were treated according to the glucose regulation protocol.
The glucose variability results for the low‐carbohydrate
group vs standard group, respectively, for continuous
glucose monitoring were 8.0 ± 1.4 vs 8.3 ± 1.5 mmol/L and
19412452, 2023, 2, Downloaded from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10960 by Western University, Wiley Online Library on [27/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
| 283
blood gas glucose 8.3 ± 1.1 vs 8.7 vs 1.3 mmol/L. The
enteral low‐carbohydrate formula showed a trend toward
reduced mean glucose during continuous glucose mon-
itoring, but no significant effect was noted on the primary
outcome of glucose variability or time in target range.26
Patients on the low‐carbohydrate formula had a signifi-
cant reduction in intravenous insulin requirements on day
2 but was not statistically significant between the two
groups throughout the study. The study acknowledged
that the duration of intervention in the study was short
and not all patients may have reached feeding goals,
which may have influenced outcomes. It also noted that
glycemic variability is dependent upon multiple factors
including severity of disease and comorbidities as well as
frequency of glucose measurements and insulin therapy.
The study noted the effect of nutrition on glucose
variability in such short duration in a broad patient
population who were critically ill make it difficult to draw
conclusions. Shao et al25 conducted a randomized prospec-
tive controlled single‐annonymized study evaluating the
impact of a diabetes‐specific formula vs a standard formula
on glycemic control in 104 patients with diagnosis of severe
acute ischemic stroke and swallowing problems. The
diabetes‐specific formula contained 750 cal/L; 32 g pro-
tein/L; 84 g carbohydrate/L; 32 g fat/L; 15 g of fiber/L (12 g
soluble; 3 g insoluble fiber). The standard formula compo-
sition included 1500 cal/L; 60 g protein/L, 185 g carbohy-
drate/L, 58.4 g fat/L, and 15 g fiber/L (7.4 g soluble and
7.6 g insoluble). Insulin infusion was initiated when
glucose levels measures >10 mmol/L. Postprandial glucose
parameters, including capillary glucose concentration for
8–16 h after EN initiation, incremental areas under the
curve, peak value, and mean glucose concentration were
significantly lower in the diabetes‐specific enteral formula
group vs the standard formula group.25 No significant
differences in incidence of hypoglycemia, glycemic varia-
bility parameters, nutrition parameters, or insulin dosing
was noted between the two groups.25 The study reported
limitations including the different energy densities of the
formulas studied. The diabetes‐specific formula required
larger feeding volumes and faster infusion rates to meet
nutrition goals which may result in increased GI
intolerance. The authors also acknowledged the short‐
term observation of the study being only 7 days. The
authors suggest that more studies are needed to investigate
if application of a diabetes‐specific formula will impact
long‐term glycemic control.25
Ojo et al27 conducted a systematic review and meta‐
analysis of randomized controlled trials evaluating the
effectiveness of diabetes‐specific formulas vs standard
formulas in managing cardiometabolic parameters in
patients with type 2 diabetes in variable settings
including diabetes center/outpatient diabetic clinics,

284 | CHURCH and ZOELLER
rehabilitation departments, ambulatory patients, nursing
home and long‐term care facilities, and ICUs. All 14
studies in the systematic review showed diabetes‐specific
formulas effectively lowered blood glucose parameters vs
standard formulas.27 Only five studies were included in
the meta‐analysis that confirmed the finding that fasting
blood glucose was significantly lower (P = 0.001) in the
diabetes‐specific formula group compared with the
standard formula group with a mean difference of
−1.15 (95% CI, −2.07 to −0.23). The sensitivity analysis,
however, showed no significant differences in fasting
blood glucose between the two groups (P > 0.05) after
removal of two studies. Glycated hemoglobin was
significantly lower (P = 0.005) in the diabetes‐specific
formula group compared with standard formula group
following meta‐analysis and sensitivity analysis.27 The
limitations of the review reported small study size and
high level of heterogeneity of the studies.27
Burslem et al23 conducted a review of evidence to
support the use of a low‐carbohydrate, high‐fat (LCHF)
enteral formula in patients who were critically ill. Studies
met criteria for inclusion in the review if the individuals
were adult patients with or without preexisting diabetes
mellitus in the critical care setting. The intervention
included an LCHF formula defined as a formula
containing ≤40% of calories from carbohydrate and
≥40% of calories from fat. All four randomized controlled
trials included had similar macronutrient distribution
and fiber content, but they all chose a different method to
measure glycemic variability.23 The review acknowl-
edged all four trials had comparable admission diagnosis
and the LCHF formulas used had similar macronutrient
distributions. Varied results were noted between all four
trials likely due to different study periods, frequency of
blood glucose measurements, and numerous measures to
calculate glycemic variability.23 Findings of the review
showed LCHF formulas may improve glycemic control in
patients who are critically ill with diabetes mellitus
and/or hyperglycemic patients. Larger randomized trials
are needed to validate these finding among different
subgroups of patients with critical illness.23
Van Steen et al26 conducted a randomized controlled
open‐label study of 101 patients who were critically
ill with or without preexisting diabetes mellitus and
received either an LCHF formula or standard formula for
a 72‐h period. The primary outcome, glycemic variability,
was measured by mean absolute glucose (MAG) change.
MAG change was not significantly different with the
LCHF formula compared with standard formula (0.8 vs
0.9 mmol/L/h; 95% CI, −0.1 to 0.1; P = 0.510). Insulin
requirements were noted to be lower throughout the
study for patients receiving LCHF but did not reach point
of statistical significance (66.1 vs 94.4 IU; 95% CI, −59.6
19412452, 2023, 2, Downloaded from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10960 by Western University, Wiley Online Library on [27/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
to 9.0; P = 2.456).26 Wewalka et al28 conducted a
randomized controlled, open‐label study with 44 patients
who were critically ill receiving an LCHF formula
(1 cal/ml; 55% carbohydrate, 15% protein, 30% fat, and
contained 1.5 g of fiber per 100 ml) vs fat‐based formula
(1 calories/ml; 37% carbohydrate, 18% protein, 45% fat,
and 2.3 g of fiber per 100 ml) over 7 days.28 Patients may
have been hyperglycemic upon admission but patients
with diabetes mellitus were excluded. Mean blood
glucose levels were significantly higher in patients who
received the LCHF formula compared with standard
formula on day 1 (143 vs 137 mg/dl; P = 0.048) but mean
blood glucose levels were not significantly different over
the next 6 days (P = 0.655).28 Doola et al29 completed a
randomized controlled, double‐annonymized trial in 41
patients who were critically ill and hyperglycemic
assigned to an LCHF formula (7.4 g carbohydrate/
100 ml) vs standard formula (14.1 g carbohydrate/
100 ml) over 48‐h.29 Blood glucose measurements were
obtained from blood gas sampling or point‐of‐care device
every 1–2 h via insulin protocol. Significant findings
included lower insulin requirements (1.01 vs 2.31 U/h;
95% CI, 0.24–2.36; P = 0.017), glycemic variability as
measured by coefficient of variation (12.6% vs 15.9%; 95%
CI, 0.6–5.6; P = 0.01) and mean blood glucose levels (157
vs 182 mg/dl, P = 0.002), in patients receiving the LCHF
formula vs the standard formula.29 Mesejo et al30
conducted a prospective, open‐label, annonymized‐
randomized, multicenter study in 157 patients who were
critically ill assigned to a new‐generation diabetes‐
specific formula (1 cal/ml with nutrient distribution
23% protein, 33% carbohydrate, 40% fats; fiber [80%
inuline/20% cellulose]), standard control formula
(1.3 cal/ml with nutrient distribution 20% protein; 48%
carbohydrate, 29% fat, fiber [50% soluble; 50% insoluble
fiber]) or control diabetes‐specific formula (1 cal/ml with
nutrient distribution 20% protein; 30% carbohydrate, 48%
fat, fiber [31% FOS]).29 Inclusion criteria: EN expected to
be >5 days; mechanical ventilation, baseline glucose
>126 mg/dl on admission or >200 mg/dl in first 48 h.
Patients with insulin‐dependent diabetes, renal, or
hepatic failure were excluded as well as patients
receiving treatment with immunosuppressants, fat‐
lowering drugs, and corticosteroids. Glycemic variability
was calculated as the standard deviation, glycemic
lability index and coefficient of variation.29 Results
showed the new‐generation diabetes‐specific formula
led to significantly lower insulin requirements (19.1 vs
23.7 IU/day, P < 0.05); mean plasma glucose (138.6 vs
146.1 mg/dl, P < 0.01); and capillary blood glucose levels
(146.1 vs 155.3 mg/dl, P < 0.001) compared with standard
formula.29 The control diabetes‐specific formula led to
only reduced capillary blood glucose levels when (150.1

NUTRITION IN CLINICAL PRACTICE
vs 155.3 mg/dl, P < 0.01) compared with standard for-
mula.29 Both diabetes‐specific formulas reduced capillary
glucose on ICU day 1 (P < 0.01), glucose variability in the
first week of ICU stay (P < 0.05), and incidences of
ventilator‐associated tracheobronchitis (P < 0.01) or
pneumonia (P < 0.05) compared with standard formula.
No significant effects based on enteral formula were
produced on hospital stay or mortality. The study
concluded that a diabetes‐specific formula in patients
on mechanical ventilation with hyperglycemia may lead
to lower insulin requirements, reduced plasma and
capillary blood glucose level, and potentially reduce the
risk of ICU acquired infections but notes that further
larger clinical trials are need to assess the capability of
these formulas to reduce risk of acquired infections in
this high‐risk group.29
The Canadian Critical Care Nutrition Guidelines
2015 report insufficient data to recommend a low‐
carbohydrate diet with insulin therapy in patients who
are critically ill.21 The 2016 ASPEN/SCCM guidelines do
not recommend the use of disease‐specific formulas in
patients who are critically ill.7 ESPEN guidelines for
HEN 2022 suggest “a modified enteral formula with
lower sugar content, containing slowly digestible carbo-
hydrates and a fat content enriched in unsaturated fatty
acid, especially monounsaturated fatty acids may be use
for patients with diabetes.”6
Before initiating EN in patients with diabetes or
hyperglycemia, clinicians should assess the patient's overall
clinical status and consider factors contributing to hyper-
glycemia, current blood glucose trends, insulin require-
ments, and level of GI function. Formula selection may also
be dependent upon formula composition and clinicians
should evaluate which formula best meets the nutrition
needs and clinical goals for their patient population.23,24 EN
goals in patients with diabetes or hyperglycemia should aim
to optimize glycemic control, minimize metabolic abnor-
malities, and prevent EN intolerances.24
Renal formulas
Renal formulations are designed to meet the needs of
patients with renal dysfunction in variable stages of disease
progression. Renal formulas are typically calorically and
nutrient‐dense, volume‐restricted with lower levels of
electrolytes (magnesium, phosphorus, potassium, sodium).
Protein concentrations may be higher or lower than
standard formulas. Formula selection may be dependent
on treatment plan, whether a patient is receiving renal
replacement therapy, presence of comorbidities, and
overall clinical status.3,31,32 Patients with acute kidney
injury (AKI), chronic kidney disease (CKD) Stages 1–5D
19412452, 2023, 2, Downloaded from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10960 by Western University, Wiley Online Library on [27/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
| 285
and posttransplant may be at risk for malnutrition, loss of
protein and energy stores, and micronutrient deficien-
cies.31 Nutrition status should be considered an important
factor in the clinical assessment of the patient and may
affect formula selection.31,32 Patients with CKD with no
plans for dialysis may benefit from a calorically dense,
volume‐restricted formula with lower levels of protein and
electrolytes (potassium, phosphorus, magnesium).16 Pa-
tients receiving dialysis may benefit from a calorically
dense, volume‐restricted, high‐protein formula and may or
may not need a reduction of potassium, phosphorus, and
magnesium.16 Clinicians should also be attentive to
micronutrient content of enteral formulas when selecting
formulas for patients with renal dysfunction. Kitabayashi
et al33 conducted a single‐center, cross‐sectional study
analyzing the effect of magnesium intakes from EN on
serum magnesium levels in 61 adult patients undergoing
hemodialysis for 41 days. Patients received an oral diet
(15%–20% protein, 20%–25% fat, and 60%–65% carbohy-
drate) or an EN formula for nutrition. Two enteral
formulas were administered as part of the study. The
high‐protein enteral formula was composed of 50 g protein;
25 g fat, 155 g carbohydrate, 1000 mg potassium, 700 mg
calcium, 700 mg phosphorus, and 300 mg magnesium per
liter. The renal formula was composed of 32.5 g protein;
28 g fat, 169 g carbohydrate, 780 mg potassium, 330 mg
calcium, 400 mg phosphorus, and 170 mg magnesium per
liter. Magnesium intake by EN resulted in higher serum
magnesium levels than the hospital diet. Multiple regres-
sion analysis showed intake of enteral formulation by tube
feeding was significantly associated with serum magne-
sium levels (Beta [B] = 0.90 [95% CI, 0.61–1.20], P < 0.01).
Patients with high magnesium levels showed increased
length of hospital stay (B = 0.24 [95% CI, 0.09−0.39],
P < 0.01). The study concluded that enteral formulation
affects serum magnesium levels in patients undergoing
hemodialysis and attention should be paid to possible
excessive elevation of serum magnesium in patients
receiving EN.33
Patients who are critically ill undergoing continuous
renal replacement therapy (CRRT) may require a
volume‐restricted formula with high protein to meet
the protein demands of therapy.7 Considerations during
CRRT include nonintentional calories (other sources of
calories) with the primary sources including substrates
used in CRRT and medications/infusions commonly
used in critical care.34 The substrates used in CRRT in
the form of lactate‐containing fluids, dextrose‐containing
fluids, and citrate‐containing fluids may also provide
additional calories.34 Medications used for sedation
during mechanical ventilation or medications for severe
hypertension may provide calories with a range
1.1–2 kcal/ml.34
 19412452, 2023, 2, Downloaded from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10960 by Western University, Wiley Online Library on [27/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
286 | CHURCH and ZOELLER

ESPEN guidelines 2021 in hospitalized patients with
acute or CKD do not recommend routine use of disease‐
specific enteral formulas.35 Use of specialized formulas
for AKI, AKI on CKD, or CKD with kidney failure
should be individualized.35 Formula selection should be
based on the calorie and protein ratio to meet the dosing
recommended in clinical practice guidelines (Table 1).
The guidelines further state “in selected patients with
electrolyte and fluid imbalances, concentrated ‘renal' EN
formulas with lower electrolyte content may be preferred
over standard formulas.”35 Formulas designed for pa-
tients with renal dysfunction are more concentrated and
consist of a lower sodium, potassium, and phosphorus
profile and may be beneficial in reaching protein goals in
patients requiring higher protein needs, patients exhibit-
ing electrolyte abnormalities, and or/fluid overload.35

TABLE 1 Recommended protein intakes in patients with renal dysfunction

CKD (stage 3–5) patient not on
dialysis without diabetes
CKD (stage 3–5) patient not on
dialysis with diabetes
Hemodialysis and peritoneal
dialysis patient without
diabetes
Hemodialysis and peritoneal
dialysis patient with diabetes
Hospitalized patient with CKD
without acute/critical illness
Hospitalized patient with AKI/
AKI on CKD, without acute/
critical illness
Hospitalized patient with AKI,
AKI on CKD, CKD with
acute/critical illness not on
hemodialysis or peritoneal
dialysis
Patient who is critically ill with
AKI, AKI on CKD, CKD with
kidney failure on intermittent
hemodialysis
Patient who is critically ill with
AKI or AKI on CKD on
continuous renal replacement
therapy
Patient who is critically ill with
acute renal failure or AKI
National Kidney Foundation
Kidney Disease Outcomes
and the Quality Initiative/
Academy of Nutrition and
Dietetics36
0.55–0.60 g/kg BW/day36 or
0.28–0.43 g/kg BW/day with
additional keto acid/amino
acid analogs to meet protein
requirements 0.55–0.6 g/kg
BW/day36
0.6–0.8 g/kg BW/day36
1.0–1.2 g/kg BW/day36
1.0–1.2 g/kg BW/day36
European Society for Clinical Society of Critical Care
Nutrition and Metabolism Medicine/American Society
Guideline for Hospitalized for Parenteral and Enteral
Patients with Acute or Nutrition Guidelines in the
Chronic Kidney Disease Adult Critically Ill Patient
202135 20167
0.6–0.8 g/kg BW/day35
0.8–1.0 g/kg BW/day35
Start with 1 g/kg BW/day and
increase up to 1.3 g/kg BW/
day35
1.3–1.5 g/kg BW/day35
1.5 g/kg BW/day up to 1.7 g/kg Up to 2.5 g/kg BW/day7
BW/day35
1.2–2.0 g/kg BW/day7

Note: Recommended protein intakes are in grams per kilogram of BW per day and determination of BW should be calculated based on clinical judgment.
Abbreviations: AKI, acute kidney injury; BW, body weight; CKD, chronic kidney disease.

NUTRITION IN CLINICAL PRACTICE
Protein should not be restricted in patients with renal
insufficiency or AKI to avoid or delay dialysis.1,5,7
The ASPEN/SCCM 2016 guidelines recommend “ICU
patients with acute renal failure (ARF) or AKI be placed
on a standard enteral formulation and that standard ICU
recommendations for protein (1.2–2 g/kg actual body
weight per day) and energy (25–30 kcal/kg/day) provi-
sion should be followed.”7 “If significant electrolyte
abnormalities develop, a specialty formulation designed
for renal failure (with appropriate electrolyte profile)
may be considered.”7 Protein recommendations for
patients receiving frequent hemodialysis or CRRT
should be increased to maximum of 2.5 g/kg/day.7 A
high‐protein standard formula with or without volume
restriction may best support patients undergoing CRRT
with routine monitoring of electrolytes to ensure the
proper formula is in place. Based on clinical guidelines,
standard formulas that meet protein targets remain the
first choice in formula selection, reserving disease‐
specific EN renal formulations for patients with signifi-
cant electrolyte abnormalities and fluid imbalances.7,35
Hepatic formulas
Hepatic formulas are designed for use in patients with
hepatic disorders. Hepatic formulas are designed to be
calorically dense, volume‐restricted, and provide a higher
ratio of branched‐chain amino acids (BCAA) which
include valine, leucine, isoleucine compared with a
decreased amount of aromatic amino acids (AAA) which
include phenylalanine, tyrosine, and tryptophan.3,5
Formulas may be low in fat with increased MCT's as an
effort to potentially minimize fat intolerance and facilitate
fat absorption in patients with steatorrhea.2(532–533)
Volume restriction may alleviate complications with
ascites and edema.3
Because of the state of metabolic unbalance and
altered hormonal activity, patients with liver failure may
have atypical BCAA/AAA ratios with increased levels of
AAAs compared with BCAAs.2,3,5,16 BCAAs are metabo-
lized in the skeletal muscles and provide the substrate for
energy production and also aid in muscle protein
synthesis.37 Increased demand for calories and protein
in patients with cirrhosis may lead to increased BCAA
utilization for glutamine production resulting in
decreased plasma BCAA levels.37 BCAA's also decrease
cerebral ammonia levels and reduce the uptake of AAA
across the blood brain barrier.2,3,5,16 Patients with
cirrhosis may have the inability to metabolize AAAs
resulting in increased in levels of AAA. Increased AAA
in the brain allows for production of false neurotrans-
mitters contributing to the neurological symptoms in
19412452, 2023, 2, Downloaded from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10960 by Western University, Wiley Online Library on [27/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
| 287
hepatic encephalopathy.2,16 Providing an EN formula
with a high BCAA to AAA ratio is hypothesized to
decrease the uptake of AAA and reduce hepatic
encephalopathy and aid in restoration of muscle
mass.1,2,5,7,16
ASPEN/SCCM 2016 enteral formula recommendations
for acute and/or chronic liver disease include using
standard enteral formulas (polymeric, isotonic, or near
isotonic 1–1.5 kcal/ml EN formula) as there is no evidence
to support BCAA formulations improve mental status or
coma grade in patients in the ICU already receiving
antibiotics or lactulose.7 ESPEN 2020 also recommends
standard whole protein enteral formulas for acute liver
failure due to the lack of evidence regarding the value of a
disease‐specific formula, including EN‐enriched formulas
with BCAA.38 In severe alcoholic steatohepatitis, enteral
formulations should meet the energy and protein require-
ments of the patient with the use of standard formulas,
preferably high‐energy density (>1.5 kcal/ml).38 Con-
versely, ESPEN does recommend enteral formulations
with BCAA's in patients with hepatic encephalopathy in
cirrhosis38 Gluud et al in a recent Cochrane Review 2017
on branched‐chain amino acids and individuals with
hepatic encephalopathy39, completed a meta‐analysis of 16
randomized clinical trials, with 97% of the 827 participants
having cirrhosis. Oral/enteral BCAA alone in patients
who were not responding to medication use showed a
beneficial effect on hepatic encephalopathy over placebo/
no intervention diets, lactulose, or neomycin in patients
who were not critically ill (Risk Ratio [RR] 0.73, 95%
Confidence Interval [CI], 0.61–0.88).39 Further trials are
needed to determine if the benefits can be transposed over
to patients who are critically ill.39 ESPEN also recom-
mends in patients with cirrhosis and encephalopathy who
is intolerant to protein, vegetable protein diets may be
beneficial.38
Standard intact‐protein formulas with consideration
for a nutrient‐dense formulation depending on the
patient's nutrition requirements and fluid status remains
first choice in formula selection.40 Volume‐restricted,
and calorically dense formulas may be indicated in
patients with ascites to minimize fluid shifts.41 Specialty
formulas may be used in cases of significant mal-
absorption (semielemental, elemental) or with other
additional comorbidities.40 Data for the use of immune‐
enhancing or BCAA formulas remains lacking.40
Pulmonary formulas
Early pulmonary formulas were designed for patients
with chronic pulmonary disease to assist with mechani-
cal ventilation weaning.3,5 The formulas consist of a

288 | CHURCH and ZOELLER
high‐fat (>50% total calories), low‐carbohydrate (<30%
total calories) ratio with the hypothesis that the altera-
tion in fat/carbohydrate composition would reduce
carbon dioxide production.3,5 The protein delivery may
or may not be increased over standard formulas.
Pulmonary formulations developed for patients with
chronic pulmonary disease contain an ω‐6 fatty acid
profile (corn and safflower oils).3 Pulmonary formulas
later evolved to include immune‐modulating properties
and an altered fatty acid composition for patients with
acute lung injury (ALI) and acute respiratory distress
syndrome (ARDS).3,5 These newly designed pulmonary
formulations contain ω‐3 fatty acids (EPA, DHA, gamma‐
linolenic acid [GLA]), and antioxidants including, but
not limited to, vitamins C, E, and A and were created
with the reputed benefit of reducing inflammation.3,5,42
Studies regarding early pulmonary formulas exhib-
ited promise in assisting patients with ventilation
weaning but studies were often small with few partici-
pants. Faramawy et al42 2014 compared outcomes in
ventilatory requirements with administration of an
LCHF enteral feed to a standard feed in 100 patients
with type 2 respiratory failure secondary to pulmonary
disease requiring mechanical ventilation. Fifty patients
received the standard feeding composed of 53.3%
carbohydrate, 30% fat, and 16.7% protein. The other 50
patients received the LCHF feed composed of 28.1%
carbohydrate, 55.2% fat, and 16.7% protein. There were
no statistically significant differences between both
groups in mean energy requirements. Outcomes showed
a significant decrease in the LCHF enteral feed group
when compared with the standard feed in arterial carbon
dioxide tension (16% vs 4%; P < 0.001) and minute
volume (8% vs 2% at weaning; P < 0.001). Duration of
mechanical ventilation was significantly decreased in the
LCHF group by 62 h vs the standard feed (P < 0.001).42
The study concluded that a nutrition regimen including a
high‐fat formula may reduce ventilatory requirements
and duration of mechanical ventilation in patients with
type 2 respiratory failure but further studies are needed
to understand the mechanisms of the effects as well as
confirmation of these findings in other patient popula-
tions who are acutely ill.42 Dushianthan et al43 2019
conducted a systematic review on the effects of im-
munonutrients in adult patients on mechanical ventila-
tion with ARDS. Patients received an enteral formula
composed of ω‐3 fatty acids (with or without glutamine
and antioxidants) or supplemental ω‐3 fatty acids and
were compared with patients receiving a standard
formula or placebo. The primary outcome measured
was all‐cause mortality and secondary outcomes
included ICU LOS, ventilator days, indices of oxygen-
ation, cardiac adverse events, and GI events.43 All studies
19412452, 2023, 2, Downloaded from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10960 by Western University, Wiley Online Library on [27/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
reported no significant differences in all‐cause mortality
with the use of ω‐3 fatty acid–enriched formulas or
additional supplemental ω‐3 fatty acids and antioxidants
compared with the standard control (RR, 0.79; 95% CI,
0.59–1.07; participants = 1015; low‐quality evidence).43
Due to low quality of evidence, the review could not
determine if immunonutrition with ω‐3 fatty acids and
antioxidants reduced ICU LOS, reduced duration of
ventilator days, improved oxygenation, or whether they
increased adverse events such as cardiac and GI.43 The
authors reported the studies were heterogeneous with
type and duration of intervention, caloric targets, and
reported outcomes. A single‐center, prospective, random-
ized, single‐annonymized controlled trial looked at the
effect of immune‐enhancing formula (LCHF formula
with EPA, GLA, and antioxidants) compared with a
standard formula in 46 patients with sepsis‐induced
ARDS.44 The immune‐enhancing formula was more
calorically dense, lower in carbohydrate composition
and higher in fat than the standard formula. The
standard formula was lower in calories per volume but
with a higher carbohydrate concentration, did not
contain EPA or GLA, and vitamins E and C were lower
than the immune‐enhancing formula. Both formulas
were administered continuously via pump and both
groups reached 70% of the estimated calorie goals within
the first week of ICU stay and achieved 100% within 14
days. No statistically significant differences or outcomes
were noted with regards to duration of mechanical
ventilation, incidence of new nosocomial infections,
changes over time in Sequential Organ Failure Assess-
ment scores, and 60‐day mortality rate.44
ASPEN/SCCM 2016 guidelines do not recommend
the use of LCHF formulations in patients who are
critically ill with acute respiratory failure.7 The guide-
lines state that although early small trials showed
promise reducing duration of mechanical ventilation
with the use of LCHF enteral formulas over standard
formulas, the findings were not replicated in later larger
randomized clinical trials.7 Due to low overall evidence
from clinical trials, no recommendation with regards to
the use of an EN formula with an anti‐inflammatory fat
profile (ω‐3 fish oils, borage oil) and antioxidants in
patients with ARDS or severe ALI can be made at this
time.7 ASPEN/SCCM 2016 recommends an energy‐dense
(1.5–2 cal/ml) volume‐restricted EN formulations may be
indicated in patients with acute respiratory failure
experiencing volume overload.7 Conversely, the Cana-
dian Critical Care Nutrition Support Guideline 2015, do
endorse the consideration for use of enteral formulas
with fish oils, borage oils, and antioxidants in patients
with ALI and ARDS.21 “There is insufficient data to
make a recommendation on the supplementation of fish

NUTRITION IN CLINICAL PRACTICE
oils alone in critically ill patients.”21 ESPEN 2019
guidelines for clinical nutrition in the ICU recommend
administration of EN‐enriched ω‐3 fatty acids within
nutrition doses, but high doses of ω‐3–enriched EN
formulas should not be given on a routine basis or be
given by bolus administration.45 ESPEN reviewed studies
that showed enteral formulas enriched in borage oil and/
or ω‐3 fatty acids administered to patients with ARDS,
ALI, and sepsis resulted with positive outcomes in terms
of LOS, length of ventilation and mortality.45 The meta‐
analysis found a trend for advantage in oxygenation for
enteral formulas enriched in EPA, GLA, and antiox-
idants. Positive outcomes were not observed when ω‐3
fatty acids and borage oil were administered as a separate
additive rather than as a component of the enteral
formula and may be associated with an increased risk
especially in higher ω‐3 fatty acid dosages.45 Continuous
administration is also preferential over bolus as bolus
showed no advantage in outcomes.45 Based on clinical
guidelines, a standard polyermeric formula or energy/
dense volume‐restricted formula for patients with respi-
ratory dysfunction experiencing volume overload, may be
first choice in enteral formula selection for patients with
pulmonary failure.45 EN‐enriched ω‐3 fatty acid formulas
may be option if administered continuously and are
composed of nutritionally safe doses of ω‐3 fatty acids.45
Immune‐enhancing formulas
Immune‐enhancing formulas are marketed as specialized
EN formulas with anti‐inflammatory properties and
immune support properties purported to improve clinical
outcomes.3 Formulas may be composed of one or more of
the following: SCFAs, ω‐3 polyunsaturated fatty acids
(EPA and DHA), glutamine, arginine, nucleic acid,
selenium, and/or antioxidants (including but not limited
to vitamins C, E, selenium, and zinc).3,5
ω‐3 fatty acids
ω‐3 fatty acids are hypothesized to have anti‐
inflammatory properties.46,47 A systematic review and
meta‐analysis of ω‐3 fatty acid supplementation or
administration of ω‐3 fatty acid containing EN formulas
in patients who were critically ill showed no significant
effects on mortality, overall hospital LOS, or complica-
tions related to infections, but noted significant reduction
in ventilator duration and critical care LOS.48 Kagan
et al49 conducted a single‐center, prospective, random-
ized, comparative, double‐annonymized‐controlled study
in patients with severe multiple trauma requiring
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| 289
mechanical ventilation. Patients were to receive either a
control formula (high‐fat; low‐carbohydrate) or a formula
enriched with EPA, GLA, and antioxidants. The two
formulas were similar in calorie, protein, and macro-
nutrient composition.49 EN was prescribed daily to meet
approximately 80% of energy requirements.49 Results
showed no significant differences for oxygenation levels
at days 4 and 8, incidence of ARDS/ALI, length of
ventilation time, duration of ICU days, and 28‐day
mortality between the two groups. The study concluded
that EN‐enriched formula with ω‐3 fatty acids failed to
improve oxygenation levels, reduce the incidence of
ARDS/ALI, or show any significant benefit in patients
with severe trauma.49 The study acknowledged that the
dosage of ω‐3 fatty acids in the enriched EN formulation
may not have met the threshold necessary to provide
clinical benefits, and therefore would not recommend this
specialized formula in the study population.49
Glutamine
Glutamine is the primary fuel for enterocytes, lymphocytes,
and macrophages.5,37,38 During stress, glutamine becomes a
conditionally essential amino acid and serves as a precursor
for glutathione, which protects against oxidative
injury.5,46,47 Gholamalizadeh et al50 completed a meta‐
analysis aimed to investigate the effect of glutamine on
inflammation markers in patients who were critcally ill
receiving EN or parenteral nutrition. Ten case‐controlled
studies showed that L‐glutamine supplementation had a
significant association with reduction in C‐reactive protein,
but no significance noted with interleukin‐6 or tumor
necrosis factor alpha.50 Shariatpanahi et al51 conducted a
randomized, double‐annonymized, placebo‐controlled trial
investigating the effects of enteral administration of
glutamine on intestinal permeability in 80 patients in the
ICU receiving EN with 0.3 g/kg/day glutamine powder or
enteral formula with maltodextrin for 10 days. The study
hypothesized that after enteral glutamine supplementation,
plasma antiendotoxin immunoglobulin, and immuno-
globulin M would be increased, whereas plasma zonulin
and endotoxin levels would decrease.51 Zonulin is a
regulator of intercellular tight gap junctions and is the
only physiological measurable blood protein that reflects
intestinal permeability.50 Increased circulating zonulin
levels may indicate impaired intestinal barrier function.51
Endotoxin is a component of the outer membrane of Gram‐
negative bacteria and breakdown of the intestinal mucosal
barrier allows endotoxins to be released into systemic
circulation.51 Results showed enteral glutamine signifi-
cantly reduced plasma zonulin concentration in the
glutamine group (P < 0.001) and noted a significantly

290 | CHURCH and ZOELLER
greater reduction in endotoxin concentration in the
glutamine group vs control (P = 0.014).51 Decreased levels
of antiendotoxin IgM and IgG antibody were observed in
the control group with an increase in the glutamine group
(P < 0.001).51 The glutamine supplementation group also
had significantly lower incidence of diarrhea (P = 0.044)
and constipation (P = 0.039). Intestinal permeability was
improved with glutamine‐supplemented EN.51 The study
showed that intestinal permeability in patients who were
critically ill could be improved after short‐term administra-
tion of a glutamine‐supplemented enteral feeding without
any other significant effect on GI complications, mortality,
or LOS in ICU.51
As noted, glutamine appears to be a promising
supplement, but large‐scale trials have suggested potential
harm including increased mortality with parenteral gluta-
mine supplementation or combinations of enteral/par-
enteral supplementation.46 Van Zanten et al52 completed a
systematic review and meta‐analysis looking at randomized
controlled trials with the use of enteral glutamine by itself in
patients who were critically ill. Eleven studies with 1079
adult patients with enteral glutamine supplementation only,
failed to show any significant reduction in hospital mortality
(RR, 0.94; 95% CI, 0.65–1.36; P = 0.74), infectious complica-
tions (RR, 0.93; 95% CI, 0.79–1.10; P = 0.39), or LOS in ICU
(weighted mean difference [WMD], −1.36 days; 95% CI,
−5.51 to 2.78; P = 0.52).52 Enteral glutamine supplementa-
tion may produce a beneficial outcome on patients with
burn injury. Patients with burns were associated with a
significant reduction in hospital mortality (RR, 0.19; 95% CI,
0.06–0.67; P = 0.010) and hospital stay (WMD, −9.16; 95%
CI, −15.06 to −3.26; P = 0.002) with enteral glutamine
supplementation; this subset analysis did not translate to
patients with trauma where no effect was noted.52
Arginine
Arginine becomes a conditionally essential amino acid
during stress also and is important for cell growth and
proliferation; wound healing; collagen synthesis; stimulates
the secretion of growth hormone, insulin, and glucagon;
and is a precursor to nitric oxide production, which
influences blood circulation and vascular tone.5,46,47 There
is much dispute around the safety of supplemental arginine
because of the potential elevation in nitrate and nitrite levels
in patients with sepsis and the hypothesis that the excess of
nitric oxide (NO) would cause increased vasodilation,
hemodynamic instability, and further aggravate complica-
tions of sepsis.53 However, during critical illness, stress, and
sepsis arginine levels are depleted, potentially related to both
impaired production and accelerated clearance.53–55 A
prospective single‐center cohort study of 109 patients with
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sepsis in the SICU/MICU showed patients with severe
sepsis had lower arginine, citrulline, and ornithine levels
than the control group.54 Arginine depletion in critical
illness causes reduction in NO production affecting blood
pressure and increased cell damage and death.53 Supple-
menting arginine may promote wound healing, increase
nitric oxide synthase production and improve micro-
circulatory blood flow, and reduce infection rates.53 Most
clinical trials evaluating the efficacy of arginine have used
immune‐enhancing formulas with the presence of other
immune modulators including, but not limited to, ω‐3/fish
oil, zinc, vitamin E, selenium.53 More clinical trials with
arginine supplementation alone are needed to determine
optimal dose, initiation, and duration of arginine to
maximize its benefits without harm or increased mortality.53
Nucleic acids and antioxidants
Nucleic acids are needed for cellular proliferation and
immunity, and aid in clearance of pathogens.5,46 Under
stress, nucleic acids may become deficient.5,46 Antiox-
idants in EN formulations are hypothesized to reduce
oxidative stress in patients with acute metabolic stress.47
Van Zanten et al56 conducted a randomized, double‐
annonymized multicenter trial providing a high‐protein
enteral formula with glutamine, ω‐3 fatty acids, and
antioxidants vs standard high‐protein formula to 301
patients on mechanical ventilation in the ICU. No
statistically significant differences were noted in new
nosocomial infections, Sequential Organ Failure Assess-
ment scores, mechanical ventilation duration, and ICU
and hospital LOS.56 After adjusting for Acute Physiology
and Chronic Health Evaluation II scores and age, a
significantly higher 6‐month mortality was noted in the
immune‐enhancing high‐protein EN vs standard high‐
protein EN (52% [95% CI, 40%–67%] vs 35% [95% CI,
22%–49%], respectively) suggesting potential harm (haz-
ard ratio of 1.57 [95% CI, 1.03–2.39; P = 0.4]).56 There are
a limited number of studies with nucleic acids and
antioxidants alone, most of the studies are conducted
with a combination with other immune modulators such
as fish oil, arginine, and glutamine. Before determining
individual use and benefit, more high‐quality random-
ized control trials are needed.
Overall recommendations with
immune‐enhancing formulas
Studies are lacking evaluating the perceived benefits of
individual pharmaconutrients in immune‐enhancing
formulas as most formulas are composed of multiple

NUTRITION IN CLINICAL PRACTICE
immune modulators and the clinical outcomes may
be a result of their synergistic effect from the
configuration of that individual formula. Wong et al57
completed a systematic review and meta‐analysis of
postsurgical clinical outcomes comparing standard
formulas to immune‐enhancing enteral formulas in
upper GI surgery including oesophagectomy, gastrec-
tomy, and pancreatectomy. Immune‐enhancing EN
administered postoperatively showed a significant
reduction in wound infection (RR, 0.59; 95% CI,
0.40–0.88; P = 0.009) and shorter length of hospital stay
(mean difference [MD], −2.92 days; 95% CI, 3.89–1.95;
P < 0.00001).57 No significant differences noted in
postoperative morbidities of interest (anastomotic leak
and pulmonary infection) and mortality between the
two groups.57 The studies evaluated had different
combinations of enteral immunonutrition. One of the
trials included in the review compared EN with
arginine, ω‐3, and RNA to a standard formula while
another trial evaluated an EN formula enriched with
EPA and GLA compared with standard formula.57
Society recommendations to support the use of enteral
formulations with immune‐enhancing properties are varia-
ble and based on reviews of current evidence in various
conditions. The 2016 ASPEN/SCCM Guidelines do recom-
mend the use of immune‐modulating enteral formulas
(arginine in conjunction with other immune modulators
including EPA, DHA, glutamine, and nucleic acid) for
patients with severe trauma, traumatic brain injury, and
postoperative patients in the SICU.7 However, immune‐
modulating formulas are not recommended for routine use
in patients with severe sepsis as arginine may pose a threat
to patients who are critically ill and hemodynamically
unstable. Immune‐modulating formulas are also not
recommended in patients in the MICU due to lack of
positive outcomes.7 ESPEN guidelines recommend post-
operative administration of immune‐enhanced formulas
enriched with (arginine, ω‐3 fatty acids, ribonucleotides) for
patients who are malnourished undergoing major cancer
surgery but states there is no clear evidence for the sole use
of these formulas over standard formulas preoperatively.58
For patients who are critically ill, due to heterogene-
ity of trials and no significant reduction in ICU LOS,
ventilation duration, organ failure or hospital mortality
compared with standard formulas, ASPEN/SCCM 2016
guidelines do not recommend the use of enteral formulas
with ω‐3 fish oils and antioxidants in patients with
ARDS and severe ALI.7 The 2015 Canadian Critical Care
Nutrition Guidelines also do not recommend the use of
fish oil supplementation by itself in patients who are
critically ill but does recommend enteral formulas with
fish oils, borage oils, and antioxidants in patients with
ARDS/ALI.21 ESPEN 2019 guidelines also recommend
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| 291
administration of EN‐enriched ω‐3 fatty acids within
nutrition doses in critically ill patients, but high doses of
ω‐3–enriched EN formulas should not be given on a
routine basis or be given by bolus administration.45 Per
ASPEN/SCCM 2016 guidelines, due to lack of effective-
ness with the use of enteral glutamine, it is not
recommended to add supplemental glutamine to the
EN regimen in patients with critical illness.7 Glutamine,
if part of an immune‐modulating formula, may be
beneficial in patients with traumatic brain injury and
patients in the perioperative stage of surgery in the
SICU.7 The Canadian Clinical Practice Guidelines 2015
also do not recommend the use of enteral glutamine or
enteral glutamine supplementation in patients who are
critically ill.21 ESPEN 2019 clinical nutrition in the ICU
guidelines recommend in patients with burns >20% body
surface area, additional enteral doses of glutamine
(0.3–0.5 g/kg/day) should be administered for 10–15 days
as soon as EN is initiated and 0.2–0.3 g/kg/day can be
administered for the first 5 days with EN and up to 15
days to aid in wound healing.45 Noted these recommen-
dations are for supplemental glutamine in addition to an
EN formulation. No recommendations were provided for
EN formulations already enriched with glutamine but
may serve as guideline for calculating the safety and
appropriate dosage/rate needed for the patient popula-
tion that may benefit from an enteral enriched glutamine
formula.45
Due to variability in structure, ratio of macronutrients/
micronutrients, and highly inconsistent individual dosage of
nutrients in enteral formulations with immune‐enhancing
properties, clinicians considering the use of immune‐
enhancing formulas should evaluate the patient's entire
clinical picture including present disease state and comor-
bidities and analyze each individual formula's composition
with evidenced‐based benefit and clinical practice guidelines
before prescribing its use.3,59
Food‐based blenderized formulas
Food‐based blenderized tube feedings (BTFs) consisting of
natural, whole‐food ingredients has increased in popular-
ity in the recent years primarily driven by consumer
demand in the HEN adult and pediatric settings. Food‐
based BTF allows clinicians and patients/caregivers
the opportunity to customize the formula to meet the
macronutrient and micronutrient requirements of the
consumer while synchronizing the patient's preferences
for “food choices” based on cultural, religious, ethical,
and individual health concerns such as allergies.60 The
rationale for use stems from perceived improvement in
feeding tolerance including bowel regularity; reduction in
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292 | CHURCH and ZOELLER

reflux, retching; improved volume tolerance; as well as
psychosocial benefit of normalized meals, patient partici-
pation in food selection and preparation, perceived health
benefits, and increased emotional/social connections.60,61
There are multiple avenues to choose from when deciding
upon a food‐based BTF regimen. Food‐based BTF (home‐
prepared or commercially prepared) can be used as the
sole‐source of nutrition to meet 100% of the nutrient needs
of the patient or may be used as a supplemental feed in
combination with commercial standard or commercially
prepared BTF.61 Home‐prepared food‐based BTF use
whole foods and liquids derived from a recipe or meal
plan.60,61 It is encouraged for patients with a desire to
use food‐based BTF work with a registered dietitian to
ensure the commercial food‐based and/or home‐prepared
food‐based BTF are nutritionally balanced meeting the
macronutrient/micronutrient needs of the patient.60–62
Considerations when developing a meal plan should
include the patient's medical status and comorbidities,
current enteral feeding regimen and tolerance, modality of
feeding, food allergies/intolerances, food preferences (life-
style, cultural, religious, health beliefs), ability to obtain
variety of foods, and equipment for blending and storage of
food to maintain safe food practices.5 Education and
ongoing coordination with a clinician experienced with
BTF is essential for success of a blenderized home regimen.5
With the increased popularity of whole‐food and
blenderized feedings in HEN, manufacturers drastically
increased the development and marketing of commercially
prepared BTF as an alternative food‐based feed that
was nutritionally consistent, convenient, and safe. The
downside of commercial food‐based BTF includes a more
costly product and may necessitate clinical documentation
of an allergy or intolerance to standard formula for
insurance coverage.61 Commercial whole‐food formulas
are composed of food‐based ingredients and are perceived
by consumers as more natural over traditional commercial
standard formulas. Commercial whole‐food formulas may
be polymeric standard formulas, semielemental partially
hydrolyzed formulas, disease‐specific, and plant‐based or
vegan. They may be nutrient‐dense or concentrated ranging
from 1.0 to 1.8 kcal/ml. Composition is variable, dependent
on manufacturer, and may or may not be organic (refer to
Table 2 for a list of common ingredients). Food‐based
BTF may contain soluble and/or insoluble fiber as well as
prebiotics. Commercial food‐based formulas may also
contain additional antioxidants or phytonutrients, which
may require clinical trials to determine the efficacy
and safety before use in the critically ill and acute care
population. Clinicians may also want to consider consulting
pharmacy to ensure no drug/nutrient interactions or
contraindications exist between the formula's antioxidants

TABLE 2 Whole‐food sources of commercial food‐based blenderized enteral formulas

Whole food formulation Carbohydrate Protein Fat Antioxidants
Plant‐Based Agave syrup Brown rice Alpha‐linolenic acid Acerola
Apples Garbanzo beans Canola oil Camu camu
Banana Green peas Coconut oil Cinnamon
Blueberries Hydrolyzed pea protein Flaxseed oil Coffee bean
Brown rice Quinoa Grapeseed oil Elderberry
Carrot Linoleic acid Ginger
Fruit juice MCT Hemp powder
Kale Olive oil Mangosteen
Mango ω‐3 fatty acid Quercetin
Peaches Safflower oil Rosemary extract
Pear Sunflower oil Turmeric
Pea starch
Potatoes
Pumpkin
Rolled oats
Spinach
Squash
Sweet potato
Zucchini
Nonplant‐based (carbohydrate, Chicken
fat, and antioxidant sources Ground beef
same as above) Eggs
Salmon
Turkey
Abbreviation: MCT, medium‐chain triglycerides.

NUTRITION IN CLINICAL PRACTICE
and the short‐term or long‐term medications the patient is
presently prescribed.
Formula selection remains dependent upon multiple
factors. The clinician is responsible for completing a
comprehensive nutrition assessment considering the
current medical status of the patient, including diagnosis
along with additional comorbidities, current and future
treatment plan, laboratory indices, degree or potential for
malnutrition, method of administration through the
EAD, insurance coverage considerations, while being
mindful of patient personal preferences including cul-
tural, religious, allergy, and tolerance issues.5,61 Method
of administration (continuous infusion via pump, gravity
drip, or bolus) is an important consideration for formula
selection.5,61 Food‐based BTF may require thinning to be
administered via gravity feed, which may reduce the
nutrition content of the feed.5,61 For patients requiring
feeding via pump, hang time may affect formula choice.
Home‐made BTF has the recommended hang time of
2 h62 and due to variability of commercial food‐based
formulas, check the manufacturer label for appropriate
hang time in an open system. Manufacturers have
recently began marketing closed system sets for acute
care hospitalizations and home. Feeding pump providers
only recommend use of commercial‐based enteral
formulations and do not advise home‐prepared food‐
based BTF.61 A cost/benefit analysis should be assessed
before making a formula decision weighing the cost of
commercial formulas and availability of medical insur-
ance coverage to cost of food and equipment required to
prepare and store home‐blended foods.
Research related to the safety and efficacy of food‐based
BTF is conflicting and lacking in the adult population with
most of the clinical trials being conducted in the pediatric
patient population. Microbial contamination is cited as a
reason both by clinicians and patients with the decision to
elect against a food‐based home‐prepared BTF regimen.
Johnson et al63 compared the microbial content at three
different time intervals (0, 2, and 4 h) of three enteral
formula combinations: standard ready‐to‐feed polymeric
commercial formula; blenderized feed with baby food; and
blenderized feed with whole food. Results showed no
Staphylococcus aureus or coliform/Escherichia coli detection
at any time point following preparation, total bacterial count
was below acceptable limits, and all formulas were suitable
for human consumption at all time points and sampling
dates.63 Although there continues to be conflicting data, it
should be noted that microbial contamination is a
risk for all patients fed enterally, and regardless of type of
EN regimen selected, sanitary practices should be followed.
Perceived benefits of BTF include improvement in
GI intolerance and bowel regularity and preservation of
healthy intestinal microbiota. Gallagher et al,64
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| 293
completed a prospective study transitioning complex
pediatric patients who were chronically ill on a
commercial standard formula to a BTF based on
Canada's Food Guide for Healthy Eating. Vomiting
significantly decreased from 76% to 53% (P = 0.015) as
well as incidence of gagging/retching from 82% to 47%
(P = 0.072).64 Stool consistency and frequency showed no
significant changes, however, the richness and diversity
of bacteria in stool samples significantly increased
(P < 0.001) with a significant reduction in the RA of
proteobacteria from pre‐BTF vs post‐BTF.53 Schmidt
et al65 conducted a multicenter, prospective, open‐label
and RCT on 118 long‐term patients, who were critically
ill with a neurological condition (ischemic stroke,
intracerebral hemorrhage, traumatic brain injury, or
hypoxic brain damage) and were enterally fed. The study
compared individuals receiving commercial real food‐
based formula vs SF for 30 days and its impact on
stooling frequency and consistency.65 The commercial
real‐food–based formula group had significant reduction
in number of watery stools (Type 7 Bristol Stool Chart)
(−61%, incidence rate ratio [IRR] = 0.39, P < 0.001).65 In
a prospective pilot study on the effect of a polymeric
plant‐based EN formula on gut microbiota fecal samples
showed plant‐based EN was well tolerated and improved
microbiota in children who were chronically ill, requir-
ing EN.55 Prior to the intervention, study participants
were on nonplant‐based enteral formula and transitioned
to plant‐based EN within 2 weeks and continued to
2 months.66 Fecal samples were taken prior to the
transition and patterns of bacterial diversity of study
participants were compared with healthy age‐matched
children.66 Before the transition, the study group had
decreased levels of commensals (eg, faecalibacterium)
and increased levels of pathogens (eg, enterococcus and
enterobacteriaceae).66 After transition to plant‐based EN
fecal samples showed microbiota similar to their healthy
controls.66
A literature review completed by Brown et al67 in
2020 evaluated outcomes of BTF on nutrition status
(weight, body mass index [BMI], and upper‐arm circum-
ference [UAC]) and nutrition adequacy in adults. Results
noted that BTF may be inadequate in calories, macro-
nutrients, and some micronutrients because of the
variability of BTF formula composition leading to decline
in weight status, BMI, and UAC.67 The studies reviewed
showed a trend toward more positive clinical outcomes
with commercial enteral formulas and suggested home‐
blended formulas may not be appropriate for adults who
are malnourished, thereby reserving home‐blenderized
EN for the stable adult patient with a clinical support
system and ability to prepare nutritionally adequate
BTF.67

294 | CHURCH and ZOELLER
ESPEN guidelines for HEN 2022 recommend a
standard EN formula or a commercially produced
“whole‐food” formula be used and advise against the
use of home‐made blenderized formulas due to safety
concerns.6 ASPEN Standards for Nutrition Support for
Home and Alternate Site Care recommend the use of
commercially available EN formulations when possible
and preparation of EN formulations should be done in a
manner that prevents contamination.68
ASPEN Safe Practices for Enteral Nutrition Therapy
201662 recommendations for BTF include:
(1) “Prepare blenderized tube feedings (BTF) using safe
food‐handling techniques and store it at refrigerator
temperature immediately after preparation. Discard
any unused portion after 24 hours.”62
(2) “Limit the hang time of blenderized tube feedings
(BTF) to 2 hours or less.”62
(3) “Give BTF only via a gastrostomy tube that is 14 Fr in
size or greater.”62
(4) “Do not use BTF in patients who do not have a
proven tolerance to bolus feeds, those who are
medically unstable, or those who lack a mature
gastrostomy site that is free of infection.”62
(5) “Involve a registered dietitian or nutrition support
clinician in the development of the BTF formula to
ensure adequate nutrient delivery.”62
(6) “Sanitize mechanical devices (e.g., blenders) used to
prepare BTF after each use with an established
protocol.”62
For those hospitals and institutions that begin to
transition to offering food‐based BTF, both commercial
and home‐prepared food‐based BTF, evidenced‐based
protocols should be developed with guidance from
reputable society practice guidelines and recommenda-
tions to ensure safe practices are in place for the
preparation, storage, and administration of food‐based
feeding. Recommendations will continue to evolve as
further research is developed in this emerging area
of EN.
Food allergies and individual dietary
practices and preferences
Prior to selecting an EN formula for a patient, clinicians
complete a comprehensive nutrition assessment evaluat-
ing the patient's diagnosis, medical treatment plan,
laboratory values, but also take into consideration a
patient's individual allergies, intolerances, and personal
dietary preferences.69 Food allergies/intolerances and
personal patient preferences including religious, ethical,
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and cultural choices may impact and curtail available
formula options.69 The product label should include if a
formula is halal or kosher and most enteral formulations
do not contain gluten or lactose.69 Recently manufactur-
ers have developed plant‐based formulas free of major
allergens to reach consumers with multiple food allergies
such as egg, corn, casein, whey, soy, and artificial
sweeteners. Hypoallergenic formulas are limited in the
adult world and semielemental and elemental formulas
consisting of partially or extensively hydrolyzed proteins
may be appropriate for individuals with allergies.
Clinicians should closely review formulas for efficacy
and tolerance by evaluating protein source, degree, and
method of hydrolysis, as well as nonprotein sources
because there is much heterogenicity among formulas.70
Differing opinions are noted with regards to use of
hydrolyzed proteins for preventing allergic reactions.70
To determine the efficacy of hydrolyzed formulas each
partially hydrolyzed formula should be evaluated sepa-
rately due to heterogenicity of formulas.70
With emergence of food‐based BTF formulas a wide
variety of options is now available for patients with
severe allergies. Most of the commercial food‐based BTFs
are low in allergenicity because of the absence of the
major common allergens in their formulations including
but not limited to milk, soy, corn, gluten, and artificial
ingredients. Home‐prepared food‐based BTF's provide an
unlimited number of formula combinations as consum-
ers can design recipes that are individualized to exclude
any allergen of concern. For patients with allergens and
strict dietary practices, clinicians should review the
ingredient list on the product label for protein source,
degree, and method of hydrolysis, nonprotein sources
of macronutrient, micronutrients, and antioxidants.70
For example, a consideration often overlooked when
selecting a formula for the vegan patient is the source of
vitamin D.
Hypocaloric: very high‐protein formulas
Decreased calorie, high‐protein EN formulas may have
been originally designed and marketed for use in patients
who are obese and critically ill, but are now being
promoted for use in patients who are critically ill that
require a lower calorie formula with a higher proportion
of calories being derived from protein. Characteristics of
these formulas include a low‐calorie to high‐protein ratio
usually consisting of 1 kcal/ml with a high percentage of
calories from protein ~37%. Hypocaloric, very high‐protein
formulas may have no fiber or soluble fiber, may or may
not have immune‐enhancing properties and may be
polymeric or semielemental. Hypocaloric nutrition has
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NUTRITION IN CLINICAL PRACTICE | 295

TABLE 3 Enteral formula indication for practice based on clinical guidelines and consensus recommendations
Enteral formula
Clinical problem Clinical practice guidelines and consensus recommendations considerations
Long‐term EN6 ESPEN Practical Guideline: Home Enteral Nutrition 2022 First line: standard formula
• Standard formula unless justification for blended tube feed is noted6 with or without fiber
• Standard commercial formula for patients receiving HEN without
diarrhea, constipation, or diabetes6
• Recommend fiber‐containing formula for diarrhea/constipation6
Diabetes6,21 ESPEN Practical Guideline: Home Enteral Nutrition 2022 First line: standard formula
• A low‐sugar enteral formula with slow digestible CHOs, enriched in
Other considerations: diabetic
unsaturated fatty acids (especially monounsaturated) may be used in
disease–specific formula
patients who have diabetes and are receiving HEN6
Canadian Critical Care Nutrition Guidelines 2015
• No recommendation in patients who are critically ill due to insufficient
data to recommend low‐CHO diets in conjunction with insulin therapy21
Gastrointestinal ASPEN/SCCM Guidelines for Adult Critically Ill Patients 2016 First line: standard formula
disorders7,11–13,72 • Recommend standard formula with EN initiation in severe acute
Other considerations:
pancreatitis7
semielemental with MCT or
∘ In EN intolerance, recommend transitioning to a small peptide formula
elemental formula
with MCT or nearly fat‐free elemental formula in moderate to severe
7
pancreatitis
ESPEN Guideline Acute and Chronic Pancreatitis 2020; Practical Guideline
Inflammatory Bowel Disease 2020; Practical Guideline Chronic Intestinal
Failure 2021
• Recommend standard formula in acute pancreatitis11
• Semielemental formula may be beneficial in severe acute pancreatitis
with malabsorption11
• Recommend semielemental formula with MCT in chronic pancreatitis if
standard formula not tolerated11
• Recommend standard formula (polymeric, moderate fat) in primary and
supportive nutrition therapy in patients with active IBD/CD11
∘ Specific EN formulations (eg, glutamine, ω‐3 fatty acids) are not
advised in IBD patients12
• Due to no significant differences found in remission rates with use of
elemental vs polymeric formulas, recommend standard ONS or EN for at
risk and current malnourished patients in CD remission12
• If EN indicated, recommend polymeric isotonic standard formula in
patients with short bowel syndrome13
ASPEN Consensus Statement 2022: When is enteral nutrition indicated?
• In severe acute pancreatitis, there is no current evidence to support the
use of a semielemental formula over a polymeric formula72
• No recommendation for immunonutrition in severe acute
pancreatitis until more supportive evidence from higher‐quality trials
is available72
• Exclusive EN may be an alternative to corticosteroid therapy for inducing
but not maintaining remission of CD in adults72
∘ With current recommendation no formula type indicated; no difference
in formula type (elemental, semielemental, polymeric) or fat content
impacted remission rates72
Pulmonary/ARDS/ ASPEN/SCCM Guidelines for Adult Critically Ill Patients 2016 First line:
ALI7,21 • Consider fluid‐restricted, energy‐dense formulas in acute respiratory standard formula
failure with volume overload7
Other considerations:
• No recommendation for specialty formulas (anti‐inflammatory fats and
• Concentrated/volume‐
antioxidants)7
restricted formula, and

(Continues)
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296 | CHURCH and ZOELLER

TABLE 3 (Continued)

Enteral formula
Clinical problem Clinical practice guidelines and consensus recommendations considerations
• Do not recommend the use of pulmonary formulas (high‐fat/low‐CHO) • Immune‐enhancing formula
in acute respiratory failure7 with fish or borage
Canadian Critical Care Guidelines 2015 oils + antioxidants
• Recommend fish oils, borage oils plus antioxidants in ALI and ARDS;
insufficient data to make a recommendation on fish oil supplementation
alone21
Critical care7,21,71,72 ASPEN/SCCM Guidelines for Adult Critically Ill Patients 2016 First line: standard polymeric
• Recommend high‐protein formula to meet protein target of 1.2–2.0 g/kg high‐protein formula with
actual body weight/day7 low fiber or no fiber; or a
• Avoid immune‐enhancing formulas in the medical ICU and disease‐ standard polymeric high‐
specific formulas in the surgical ICU7 protein low‐energy dense
∘ Disease‐specific, fluid‐restricted formulas may be used with persistent formula (1 kcal/ml); 37%
electrolyte abnormalities and volume restriction7 kcal from protein
• Recommend mixed fiber formulas not be used to promote bowel
Other considerations:
regularity or prevent diarrhea7
• Concentrated,
• Mixed fiber formula may be indicated in persistent diarrhea
• Volume‐restricted or disease‐
∘ If no response to fiber or malabsorption suspected, trial a semielemental
specific formula,
formula7
• Mixed fiber
• Avoid both soluble and insoluble fiber if risk for bowel ischemia or severe
• Semielemental formula
dysmotility7
ASPEN Consensus Statement 2022: When is enteral nutrition indicated?
• Recommend a 1.0–1.2 kcal/ml, higher‐protein, low‐fiber EN formula
(semielemental and polymeric formulas are tolerated) for patients
receiving vasopressor support72
ASPEN Guidelines for Adult Critically Ill Patients 2021
• EN to support energy intakes between the range 12–25 kcal/kg in the first
7–10 days of ICU admission: protein intakes 1.2–2.0 g/kg/day71
ASPEN/SCCM Guidelines for Adult Critically Ill Patient 2016
• Recommend high‐protein, hypocaloric feeding in ICU patients with
obesity
∘ 65%–70% target energy requirements as determined by IC7
∘ Weight‐based equations if no IC available7
▪ Calorie provision in range of 11–14 kcal/kg actual body weight per
day (BMI, 30–50) and 22–25 kcal/kg ideal body weight per day (BMI,
>50); protein provision in range of 2 g/kg ideal body weight (BMI,
30–40) and 2.5 g/kg ideal body weight (BMI, ≥40)7
Canadian Critical Care Guidelines 2015
• Recommend intentional underfeeding of calories (not protein) with
low–nutrition risk patients; does not apply to high–nutrition risk patients21
Canadian Critical Care Guidelines 2015
• Recommend standard formula with EN initiation18
• No recommendation regarding composition of EN in patients who are
critically ill due to insufficient data21
∘ High‐fat/low‐CHO; low‐fat/high‐CHO; high protein vs low protein21
• Do not recommend arginine and other selected nutrients21
• Insufficient data to recommend routine use of fiber (soluble or insoluble)
in enteral formulas18
• Use of enteral glutamine is not recommended21
• No recommendations for use of ornithine ketoglutarate for burn and
other patients who are critically ill due to insufficient data21
Renal failure7,35 ASPEN/SCCM Guidelines for Adult Critically Ill Patients 2016 First line:
• Recommended standard formula in acute kidney injury/acute renal standard formula
failure
Other considerations:
• Renal formula
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NUTRITION IN CLINICAL PRACTICE | 297

TABLE 3 (Continued)

Enteral formula
Clinical problem Clinical practice guidelines and consensus recommendations considerations
∘ Recommend a renal formula with appropriate electrolyte profile in • Extremely high–protein
patients with persistent abnormal electrolytes until electrolytes formula; ~37% kcal from
stabilize7 protein
• Recommend formula with an appropriate protein and electrolyte profile
to meet protein goal up to 2.5 g/kg/day in patients undergoing CRRT7
ESPEN Guidelines Patients with Acute and Chronic Kidney Disease 2021
• Recommend standard formula to meet protein goals based on disease
state
∘ A concentrated “renal” formula with lower electrolyte content may be
indicated with electrolyte and fluid imbalances35
Hepatic failure7,38 ASPEN/SCCM Guidelines for Adult Critically Ill Patients 2016 First line: standard formula
• Recommend standard formula in ICU patients with acute and chronic
Other considerations:
liver disease7
• Energy‐dense standard
ESPEN Practical Guideline in Liver Disease 2020
formula
• Recommend standard formula in acute liver failure; no evidence
• Plant‐based
enriched BCAA formulas improve outcomes38
blenderized EN38
• Recommend standard formula high in energy density ≥1.5 kcal/ml for
• Hepatic BCAA‐enriched
alcoholic steatohepatitis38
formula
• In select patients with encephalopathic cirrhosis with protein intolerance,
vegetable protein or BCAA (0.25 g/kg/day) should be used by oral route38
• Recommend long‐term BCAA‐enriched formulas (0.25 g/kg/day) in
advanced cirrhosis38
• Recommend BCAA‐enriched formulas in hepatic encephalopathy38
Trauma/TBI/surgery/ ASPEN/SCCM Guidelines for Adult Critically Ill Patient 2016 First line: high‐protein standard
sepsis7,58 • Recommend high‐protein polymeric formula in hemodynamically stable formula
patients with trauma within 24–48 h of injury7
Other considerations: standard
∘ Consider immune‐enhancing formulas with arginine and fish oil in
formula with EPA/DHA
patients with severe trauma 7
supplement
• Recommend immune‐enhancing formula with arginine or EPA/DHA
supplement with standard formula in patients who are being treated for
a TBI7
• Recommend routine use of immune‐enhancing formula with both
arginine and fish oil in postoperative surgical ICU patients7
• Recommend against use of immune or metabolic‐modulating formulas
(arginine with other agents [EPA, DHA, glutamine, and nucleic acid]) in
sepsis7
ESPEN Practical Guideline: Clinical Nutrition Surgery 2021
• Recommend standard whole protein formula for most postoperative • Immune‐enhancing formula
patients58 with arginine and fish oil
∘ Recommend enriched EN with arginine, ω‐3 fatty acids, ribonucleotides be • Immune‐enhancing formula
given perioperatively and postoperatively in patients who are with arginine, ω‐3 fatty acids,
malnourished and have major surgical cancer58 ribonucleotides
Abbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ASPEN, American Society for Parenteral and Enteral Nutrition; BCAA,
branched‐chain amino acids; BMI, body mass index; CD, Crohn's Disease; CHO, carbohydrate; CRRT, continuous renal replacement therapy; DHA,
docosahexaenoic acid; EN, enteral nutrition; EPA, eicosapentaenoic acid; ESPEN, European Society for Clinical Nutrition and Metabolism; h, hour; HEN,
home EN; IBD, inflammatory bowel disease; IC, indirect calorimetry; ICU, intensive care unit; MCT, medium‐chain triglyceride; ONS, oral nutrition
supplement; SCCM, Society of Critical Care Medicine; TBI, traumatic brain injury.

become standard of practice for patients who are critically determined by indirect calorimetry or 11–14 kcal/kg actual
ill and obese as recommended in clinical guidelines by body weight if the BMI is 30–50 and 22–25 kcal/kg ideal
multiple societies. The ASPEN/SCCM 2016 guidelines body weight or BMI > 50. Protein recommendations are
recommend providing 60%–70% of energy needs 2.0 g/kg ideal weight for the BMI of 30–40 and 2.5 g/kg

298 | CHURCH and ZOELLER
ideal weight for BMI > 40.7 ASPEN 2021 clinical guide-
lines recommend providing EN to meet calorie targets
between 12 and 25 kcal/kg for the first 7–10 days of ICU
stay.71 No significant differences were noted in patients
receiving higher vs lower levels of energy intakes in
clinical outcomes.71 Protein targets remain consistent with
the ASPEN/SCCM 2016 guidelines of 1.2–2.0 g/kg/day.71
If a patient is on vasopressor support, a 1.0–1.2 kcal/ml,
higher‐protein, low‐fiber formula is recommend and both
semielemental and polymeric formulas are appropriate.72
Energy from nonnutrition sources and noninten-
tional calories, such as fat‐based medications, medica-
tions for fluid resuscitation with dextrose, and substrates
from continuous replacement renal therapy pose a
challenge to meeting protein targets in critical care.5,26
To meet the protein needs in the patient who is critically
ill a hypocaloric, very high‐protein formula may be
indicated. Caution must also be taken in patients with
critical illness and formula selection with regards to
fiber, ASPEN/SCCM 2016 clinical guidelines do not
recommend use of soluble and insoluble fiber if there is
concern for bowel ischemia or severe dysmotility.7
CONCLUSION
Enteral formula selection can be challenging for
clinicians with innumerable formulations being devel-
oped in today's market promoting health benefits with
limited evidence‐based research to support the effec-
tiveness of the marketed pharmacological properties of
the new formulations. Clinicians need to be conscien-
tious and educated on the vast number of formula
options available to help assist patients select the proper
formula to meet their nutrition goals. Clinicians also
need to be aware of formulation changes, product
shortages, and discontinuations. Despite the expansive
diversity of formula options available, standard poly-
meric formulas continue to be the standard of practice
and first choice for most patients at all levels of
care (critical care, acute care, and home care).6,7,44 If
the standard polymeric formula is unable to achieve
desired clinical outcomes or a noted intolerance
develops, trialing semielemental, immune‐modulating,
or disease‐specific formulas may be warranted.
Conducting a comprehensive nutrition assessment
including disease state with underlying comorbidities,
treatment plan, level of GI function, review of labora-
tory indices, and patient preferences continues to be
essential to determine the best formula to meet the
patient's nutrition needs.5 Clinicians should also con-
tinue to seek quality research and reference evidence‐
based clinical guidelines from reputable EN support
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societies for assistance in appropriate formula selection
and to validate the efficacy and safety of specialty
enteral formulations3 (Table 3).
A U T H O R C O N TR I B U T I O N S
April Church conceived, designed the research, and
drafted the article. April Church and Steph Zoeller
critically revised the article, agree to be fully accountable
for ensuring the integrity and accuracy of the work, and
read and approved the final article.
C O NF L I C T O F I N T E R E S T S TA T E M E N T
None declared.
ORC ID
April Church http://orcid.org/0000-0002-0360-1413
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How to cite this article: Church A, Zoeller S.
Enteral nutrition product formulations: a review of
available products and indications for use. Nutr
Clin Pract. 2023;38:277‐300. doi:10.1002/ncp.10960