The n e w e ng l a n d j o u r na l of m e dic i n e

Review Article

Nutrition in Medicine
Dan L. Longo, M.D., Editor

Malnutrition in Adults
Tommy Cederholm, M.D., Ph.D., and Ingvar Bosaeus, M.D., Ph.D.​​

M
alnutrition is an imbalance between the growth and break- From Clinical Nutrition and Metabolism,
down of body tissues and nutrient stores, resulting in loss of muscle and Department of Public Health and Caring
Sciences, Uppsala University, Uppsala
organ mass, diminished physical and mental functioning, and impaired (T.C.), Clinical Geriatrics, Department of
clinical outcomes. Over the past 50 years, malnutrition has been increasingly rec- Neurobiology, Care Sciences and Society,
ognized as a deleterious consequence of chronic and acute disease. On the basis Karolinska Institutet, Stockholm (T.C.),
Theme Inflammation and Aging, Medical
of the cause of malnutrition, three subtypes are recognized: disease-related mal- Unit Aging, Karolinska University Hospi-
nutrition in the absence of underlying inflammation, disease-related malnutrition tal, Stockholm (T.C.), and the Depart-
with underlying inflammation, and starvation due to inadequate access to food ment of Internal Medicine and Clinical
Nutrition, University of Gothenburg, Go-
(i.e., food insecurity) (Fig. 1).1,2 thenburg, and the Clinical Nutrition Unit,
Sahlgrenska University Hospital, Gothen-
burg (I.B.) — all in Sweden. Dr. Cederholm
Pathoph ysiol o gy can be contacted at t­ ommy​.­cederholm@​
­uu​.­se or at Department of Public Health
The concept of two major pathophysiological pathways of malnutrition is well estab- and Caring Sciences, Uppsala University,
lished. The inflammation-related pathway results from anorexia and increased tissue Box 564, 751 22 Uppsala, Sweden.

breakdown, and the deficiency-related pathway is initiated by decreased intake or N Engl J Med 2024;391:155-65.
absorption of food and nutrients (Fig. 2).1,2 DOI: 10.1056/NEJMra2212159
Copyright © 2024 Massachusetts Medical Society.

Energy and Nutrient Deficiencies

Inadequate intake or absorption of energy and nutrients is the classic scenario of
malnutrition. Dysphagia after stroke and short bowel syndrome are examples of
this noninflammatory pathway. Under such conditions, human metabolism adapts
by decreasing resting energy expenditure, heart rate, body temperature, and spon-
taneous physical activity. Glycogen stores in the liver and muscles are depleted
within 1 to 2 days and replaced by body fat as the main energy source. Protein
stores are partially protected, but muscle is still depleted to ensure a supply of
amino acids for protein synthesis and oxidation for energy. This adaptation con-
tributes to the ability to survive starvation. Historical observations indicate that
survival for up to 60 days in a state of complete starvation is possible if fluids are
available.3

Inflammation-Driven Disease-Related Malnutrition

When the underlying disease is accompanied or driven by inflammation that is
mediated by inflammatory cytokines and prostaglandins, as in cancers, infections,
end-stage organ disease, or critical illness, metabolism becomes more complex
and maladaptive.4,5 In contrast to energy expenditure with pure food deprivation,
resting energy expenditure increases with food deprivation and inflammation. The
resting heart rate and body temperature increase. Protein breakdown in skeletal
muscle increases.6 Amino acids from muscle are used as fuel for the production of
glucose through gluconeogenesis and for the synthesis of proteins such as acute-
phase reactants. During inflammation, protein turnover is not regulated by nutri-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

At risk for malnutrition

Malnutrition in Adults

Disease-related malnutrition Disease-related malnutrition Malnutrition or undernutrition

with inflammation without inflammation without disease

Related to acute disease Related to socioeconomic

Related to chronic disease Related to malnutrition
or injury or psychological factors

Cancer cachexia or other

disease-specific cachexia

Figure 1. Diagnostic Overview of Malnutrition in Adults and Malnutrition Subcategories.

Malnutrition in adults is confirmed according to phenotypic and etiologic criteria in persons who are identified through screening
as being at risk for possible malnutrition. The three subtypes of malnutrition in adults are classified according to their underlying cause:
disease-related malnutrition in the absence of underlying inflammation, disease-related malnutrition with underlying inflammation, and
starvation due to inadequate access to food (i.e., food insecurity).

ent requirements but continues even when suf- according to the type and stage.11 Cancers of the
ficient energy and protein are supplied. The result upper gastrointestinal tract lead to malnutrition
is loss of muscle mass. Nutritional intake in early, whereas in breast, lung, and renal can-
acutely ill older patients is substantially reduced cers, malnutrition occurs with more advanced
when the concentration of C-reactive protein disease. Severe trauma, burns, and acute infec-
(CRP) exceeds 30 mg per liter.7 Many chronic tions trigger excessive inflammation, which
diseases are associated with low-grade inflamma- rapidly degrades fat, muscle, and organ tissue.
tion, such as chronic obstructive pulmonary dis- In patients with Crohn’s disease or celiac dis-
ease (COPD), Crohn’s disease, kidney failure, ease, malabsorption with weight loss and mal-
chronic pancreatitis, and various cancers in which nutrition are the main manifestations of the
CRP concentrations are just above the upper limit disease.
of the normal range. Slow, continuous tissue ero- In most end-stage chronic diseases of major
sion and blunted responses to nutritional treat- organ systems, inflammation-driven malnutri-
ments are well-known consequences of such long- tion eventually occurs. Malnutrition develops in
term exposure.8 20 to 50% of patients with COPD,12 congestive
heart failure,13 liver cirrhosis,14 or chronic kidney
failure.15 Patients with certain neurologic disor-
Epidemiol o gy of M a l nu t r i t ion
ders (e.g., dysphagia after stroke or Parkinson’s
As expected, the prevalence of malnutrition var- disease) and those with psychiatric or cognitive
ies according to age, the underlying disease, disorders have a similar risk of malnutrition,
and the setting.9 In the population of persons which is mainly related to reduced food intake
who are older than 65 years of age, malnutrition for noninflammatory reasons. Alzheimer’s dis-
is found in 5 to 10% of community-dwelling ease is associated with malnutrition from vari-
persons, 20 to 40% of hospitalized patients, and ous causes in 20 to 30% of cases.16 In addition,
up to 50% of nursing home residents.10 Among half of patients with major depressive disorder
patients with cancer, the prevalence varies widely lose weight.17

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 Malnutrition in Adults

R ec o gni zing M a l nu t r i t ion

Disease
Screening for Malnutrition Risk
Screening for possible malnutrition is recom-
Symptoms mended within the first 24 to 48 hours after
affecting Inflammation Catabolism
nutrition admission to a hospital or nursing home. A
number of screening tools are available35 that
typically classify persons as at risk or malnour-
Low intake
Tissue
ished on the basis of two or three criteria (Ta-
wasting ble 1). For hospitalized patients, the Nutritional
Risk Screening 2002 tool,27 the Malnutrition
Figure 2. Two Pathways of Disease-Related Malnutrition. Universal Screening Tool,26 the Short Nutritional
Malnutrition with underlying disease develops through Assessment Questionnaire,26 and the Malnutri-
two parallel and partly intertwined pathways. In the ab- tion Screening Tool25 provide rapid assessment
sence of inflammation, symptoms affecting nutrition
of nutritional risk. The Mini Nutritional Assess-
(e.g., appetite loss, dysphagia, and malabsorption) re-
sult in low food intake and reduced assimilation. With ment–Short Form30 is adapted to assess the risk
inflammation, muscle and fat breakdown increases of malnutrition among older persons. The dis-
and results in tissue loss. Inflammation also often in- tinction between the risk of malnutrition (e.g.,
duces loss of appetite that may decrease intake as well. weight loss or underweight) and risk factors for
malnutrition (e.g., loss of appetite or illness) is
gaining new attention.36
C onsequence s of M a l nu t r i t ion For patients in the intensive care unit, who
typically require immediate nutritional care,
Decreased muscle strength and mass (i.e., sarco- conventional screening tools are usually not ap-
penia) is a major disabling complication of dis- plicable. Still, the Nutrition Risk in the Critically
ease-related malnutrition, with subsequent mo- Ill score has been shown to have prognostic
bility limitations, falls, and fractures.18 In older value.37
people, frailty is increased.19 Immunodeficien-
cies and resulting infections occur early in the Assessment for Diagnosis
course of malnutrition. The rapid turnover of Other diagnostic approaches, not necessarily
immune cells requires high energy and nutrient called screening tools, are generally more com-
supplies. T-cell dysfunction resembles that seen plex and combine more measures15,28,29,31-33,38
in human immunodeficiency virus infection and (Table 1). Examples are the Subjective Global
acquired immunodeficiency syndrome. B-cell dys- Assessment (SGA)28; the Patient-Generated SGA,
function attenuates humoral antibody produc- which is mainly for patients with cancer29; and
tion. Such effects are likely to have contributed to the Academy of Nutrition and Dietetics–Ameri-
the high incidence of death from coronavirus can Society for Parenteral and Enteral Nutrition
disease 2019 (Covid-19) among older persons re- Indicators to Diagnose Malnutrition approach.38
siding in nursing homes.20 Micronutrient defi- All methods use a mixture of similar phenotypic
ciencies, including deficiencies in vitamins B1, and etiologic criteria, with criteria combinations
B6, B12, and D, folic acid, and essential n−3 and and cutoff variations leading to differences in
n−6 fatty acids, have specific deleterious effects.21 prevalence estimates.39
Depression was an unexpected observation in
young men voluntarily exposed to semistarva- Global Leadership Initiative on Malnutrition
tion in the Minnesota Starvation Experiment of In 2019, four major international clinical nutri-
the mid-1940s.22 tion societies unveiled the Global Leadership
In addition to the humanitarian costs, mal- Initiative on Malnutrition (GLIM) criteria to
nutrition has high societal costs.23 In recent years, bring together existing tools for diagnosing
awareness of the harmful effects of malnutrition malnutrition,34 with the goal of establishing a
and the often unmet nutritional needs of pa- consensual diagnostic process for global use.
tients and older adults has led to a plea to con- The two-step procedure involves initial use of a
sider clinical nutrition a human right.24 sensitive screening tool to identify persons at

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 Table 1. Major Screening, Assessment, and Diagnostic Tools for Malnutrition in Adults.*

158
Tools (Year) Phenotypic Variables Cause

Low Low Disease

Appetite Low Muscle Food Burden or
Weight Loss Loss BMI Mass Intake Inflammation Other
Screening
MST25 (1999) >2 lb (1 kg) Yes — — — —
MUST26 (2000) >5% in the past 3–6 — <20 — Yes Yes
mo
NRS27 (2002) >5% — <20.5 — Yes Yes
SNAQ26 (2005) >3 kg in the past 1 mo Yes — — — —
or >6 kg in the past
6 mo
Assessment and diagnosis
The

SGA28 (1987) >5% in the past 6 mo Yes — Yes Yes Yes Reduced function
Patient-Generated SGA29 (1995) >2% in the past 1 mo Yes — Yes Yes Yes Reduced function
MNA30 (1999) >1 kg in the past 3 mo Yes <23 — Yes Yes
MNA–Short Form30 (2001) >1 kg in the past 3 mo Yes <23 — Yes Yes
Definition of cachexia31 (2008) >5% in the past 1 yr Yes <20 Yes — Yes Elevated serum CRP
15

n engl j med 391;2

Definition of protein energy wasting >5% in the past 3 mo — <23 Yes Yes CKD Low serum albumin, low
(2008) or >10% in the past body fat
6 mo
Definition of cancer cachexia32 (2011) >5% in the past 6 mo — <20 Yes — Cancer

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or >2% if low BMI
n e w e ng l a n d j o u r na l

AAIM38 (2012) >1–2% in the past — — Yes Yes Yes Fluid retention, reduced
of

1 wk function
or >5% in the past
1 mo

July 11, 2024

ESPEN33 (2015) >5% in the past <3 mo — <20/22† Yes — —
or >10% in the past
m e dic i n e

>3 mo
GLIM34 (2019) >5% in the past <6 mo — <22/20/18.5† Yes Yes Yes

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or >10% in the past
>6 mo

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* AAIM denotes Academy of Nutrition Dietetics (AND)–American Society for Parenteral and Enteral Nutrition (ASPEN) Indicators to Diagnose Malnutrition, BMI body-mass index (the
weight in kilograms divided by the square of the height in meters), CKD chronic kidney disease, CRP C-reactive protein, ESPEN European Society for Clinical Nutrition and Metabolism,
GLIM Global Leadership Initiative on Malnutrition, MNA Mini Nutritional Assessment, MST Malnutrition Screening Tool, MUST Malnutrition Universal Screening Tool, NRS Nutritional

The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society.
Risk Screening, SGA Subjective Global Assessment, and SNAQ Short Nutrition Assessment Questionnaire.
† According to ESPEN and GLIM, the BMI cutoff is 22 for persons 70 years of age or older and 20 for persons younger than 70 years of age. GLIM also adjusts its BMI cutoffs for differ-
ences in ethnic group (i.e., for Asian persons, the BMI cutoffs for persons in those age groups are <20 and <18.5, respectively).
 Malnutrition in Adults

risk for malnutrition, followed by confirmation current obesity pandemic may limit the use of
of the diagnosis in persons with apparent mal- BMI in regions with a high prevalence of over-
nutrition. GLIM recommends mandatory assess- weight and obesity.40,41 In addition, thresholds
ment of three phenotypic criteria — weight loss, for underweight are lower in Asian persons than
low body-mass index (BMI), and low muscle in other populations.
mass — and two etiologic criteria — decreased Initially, GLIM was criticized as a new con-
food intake or food assimilation and a high dis- cept that was introduced without solid valida-
ease burden, as indicated by the presence of tion. Approximately 4 years after the introduc-
persistent or recurrent inflammation (Fig. 3). tion of the criteria, PubMed listed more than 300
Simultaneous fulfillment of at least one pheno- observational and validation studies of varying
typic and one etiologic criterion confirms the quality and more than 10 systematic reviews and
diagnosis. The malnutrition is classified as meta-analyses. Criterion validity, tested mainly
moderate or severe, depending on the degree of with the SGA as the comparator, appears to be
aberration in the phenotypic criteria. Finally, satisfactory,42 and predictive validity is good,
malnutrition can be categorized according to with overall survival being the most common
cause: disease-related malnutrition with inflam- outcome assessed.43 Nevertheless, continuous im-
mation, disease-related malnutrition without provement of the method is needed. Guidance on
perceived inflammation, or malnutrition in the the use of the muscle mass and inflammation
absence of disease (i.e., starvation) (Fig. 1). criteria has recently been provided.44 Because
The GLIM criteria combine nutrition-related technical devices for measuring body composi-
variables, including BMI, that are validated sepa- tion are not usually available, measurement of
rately on the basis of their prognostic value. The calf circumference and trained physical exami-
nation are approved methods for estimating
muscle mass. It has also been suggested that
clinical judgment about disease burden and in-
Risk Screening
flammation does not always require laboratory
For the identification of patients at risk for malnutrition,
use existing sensitive screening tools confirmation.34 The fact that the choice of screen-
ing method leads to unjustified variations in the
prevalence of malnutrition warrants thorough
Diagnostic Assessment consideration.36
Phenotypic criteria
Involuntary weight loss International Diagnostic Classification
Low body-mass index
Low muscle mass The International Classification of Diseases, 11th Revi-
Etiologic criteria sion (ICD-11), currently lacks a clinically relevant
Reduced food intake or assimilation
Disease burden or inflammatory condition diagnostic code for malnutrition in adults. More
than 40 national clinical nutrition societies with
global reach, together with the Swedish National
Diagnosis of Malnutrition Board of Health and Welfare, submitted a pro-
Requires fulfillment of at least one phenotypic criterion posal to the World Health Organization in 2020
and one etiologic criterion
to fill this gap.45 The proposal is based on the
consensus in the clinical nutrition community
that malnutrition in adults is diagnosed by
Severity Grading
means of a combination of phenotypic and etio-
Severity determined on the basis of phenotypic criteria
logic criteria.

Figure 3. Global Leadership Initiative on Malnutrition

(GLIM) Approach to Screening, Diagnosis, and Grading T r e atmen t of M a l nu t r i t ion
of Malnutrition.
Assessment for Nutritional Treatment
After risk screening, persons identified as being at risk
for malnutrition should undergo diagnostic evaluation A thorough nutritional assessment is recom-
according to three phenotypic and two etiologic criteria. mended to facilitate an individualized nutritional
If one of each is fulfilled, the diagnosis is confirmed. treatment program.46 This assessment should in-
clude the medical history (coexisting conditions),

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 The n e w e ng l a n d j o u r na l of m e dic i n e

social and psychological history (living condi- negative acute-phase reactants and should not
tions and factors such as loneliness and depres- be used as indicators of nutritional status.47
sion), and nutritional history (dental status and Serum insulin-like growth factor 1 may indicate
factors such as difficulty chewing and dyspha- anabolic activity. The serum creatinine level
gia), if the appropriate sources of information may reflect muscle mass if renal function is
are available. Meal observations, as well as re- intact.48
cords and recall of food intake, should be con-
sidered. Physical examination should include an General Aspects of Nutritional Therapy
estimate of muscle mass44 and fat mass. Coexist- A regular oral diet or medical nutrition is used
ing sarcopenia,18 sarcopenic obesity,40 or frailty19 to compensate for inadequate energy and nutri-
should be noted. Laboratory measurements that ent intake.1,2 Medical nutrition consists of modi-
are usually performed for other reasons and may fied therapeutic diets, such as fortified foods
provide nutritional information include hemo- and oral nutritional supplements; enteral nutri-
globin, liver function, lipids (e.g., serum choles- tion (tube feeding); and parenteral nutrition.1,2
terol levels, which are usually decreased with The effect of nutritional therapy depends on the
inf lammation and malnutrition), and CRP (the mechanism underlying malnutrition. When food
preferred biomarker of inflammatory activity). intake is inadequate, the supply of energy and
Visceral proteins such as serum albumin are nutrients usually restores nutritional status,

Sufficient oral intake?

No Yes

Provide energy- and protein-enriched Provide hospital food

food Perform regular follow-up
Adjust texture of food if needed
Provide oral nutritional supplements

Sufficient oral intake?

No Yes

Does the patient have a functional Continue treatment

gastrointestinal tract? Perform regular follow-up

No Partly Yes

Provide parenteral Provide a combination Provide enteral tube

nutrition of oral or enteral nutrition feeding with oral feeding
with parenteral nutrition when possible

Figure 4. Algorithm for Nutritional Support.

First-line therapy for insufficient oral intake is the provision of nutritional counseling, modified food, oral nutritional
supplements, or all three. If first-line therapy is insufficient or not feasible, enteral or parenteral nutrition is provided.

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 Malnutrition in Adults

whereas the anabolic response is limited when Until recently, young and old people were con-
inflammatory mechanisms predominate.8 sidered to have the same requirement — 0.8 g of
The general indication for enteral or paren- protein per kilogram per day — on the basis of
teral nutrition is inadequate nutrient intake for a short-term nitrogen balance studies.58 With a
week or more, whereas in critical care, nutri- new understanding of age-related changes in
tional needs must be met promptly. In general, metabolism, immunity, hormone synthesis, and
the preferred choice is enteral nutrition49 (Fig. 4), progressive frailty with age, protein require-
which requires a functioning gut. Enteral nutri- ments of 0.8 to 1.2 g per kilogram per day in
tion improves gut barrier functions, and it is healthy adults, 1.2 to 1.5 g per kilogram per day
associated with fewer infectious and metabolic in acutely ill patients or well-nourished patients
complications than parenteral nutrition. A small after surgery, and 1.5 to 2.0 g per kilogram per
proportion of patients require total parenteral day or even higher in patients with burns or
nutrition. multiple trauma are now widely recommended
but remain controversial.51,52,54-57,59 In patients
Evidence Base for Nutritional Treatment with impaired protein utilization, such as those
Numerous studies of nutritional therapy have been with hepatic or renal insufficiency (estimated
conducted. Complex patient populations, lack of glomerular filtration rate, <30 to 40 ml per min-
consensus on outcome variables, blinding diffi- ute per 1.73 m2 of body-surface area), the recom-
culties, inadequate funding, and other factors mendations are lower.60
make it challenging to conduct high-quality ran-
domized, controlled trials according to the re- Oral Treatment
quirements for pharmacologic trials. Nutritional Food intake is facilitated by nutritional counsel-
therapy trials are usually conducted in the context ing (preferably provided by dietitians); assistance
of underlying diseases, which further complicates with eating for disabled persons; modification
the interpretation of results. As a consequence, of texture, especially for those with dysphagia;
the evidence base for nutritional therapies has and food fortification with energy (preferably
been inconsistent.50 Recently, however, it has been nontropical vegetable oils) and protein for “small
strengthened by major studies and meta-analyses eaters.” The volume of food taken orally should
(discussed below). be adjusted to accommodate the amount of nu-
trients needed.61
Energy and Protein Requirements Energy and protein can also be provided in
Patients with malnutrition who are not critically fortified oral nutritional supplements: the typi-
ill often have functional impairments that re- cal amounts are 200 to 300 kcal and 10 to 20 g
duce energy expenditure, whereas other nutrient of protein per 100 ml.61 Even in light of the
requirements are generally unchanged.51,52 Indi- difficulties in conducting flawless randomized,
rect calorimetry, a preferred method for measur- controlled trials of nutrition interventions, the
ing energy requirements,53 is usually not avail- EFFORT62 and NOURISH63 trials provide solid
able outside intensive care units. On the basis of evidence of the positive clinical effects of oral
expert consensus, the estimated energy require- nutritional supplements. The EFFORT trial ran-
ment is 30 kcal per kilogram of body weight per domly assigned more than 2000 medical inpa-
day in mobile persons with limited physical ac- tients to individualized nutritional counseling
tivity and 25 kcal per kilogram per day in bed- and support or standard hospital food. Energy
ridden patients.51,52 For hospitalized and criti- and protein intakes were increased in the inter-
cally ill patients, the expert consensus–based vention group as compared with the control
recommendation is 70 to 75% of calculated en- group, and at 30 days, functional capacity was
ergy requirements (i.e., 18 to 20 kcal per kilo- improved, and readmission rates and mortality
gram per day), especially in the first phase of were reduced. Subgroup analyses indicated that
treatment.51,52,54-56 patients with cancers also benefit from the in-
Protein requirements are the subject of con- tervention.64
siderable debate in the nutrition community.57 The NOURISH trial, which involved 600 dis-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

charged patients with various diseases who Parenteral Nutrition

were malnourished, showed that a 3-month Parenteral nutrition provided through a periph-
course of oral nutritional supplements was as- eral or central venous catheter is indicated when
sociated with almost a 50% reduction in mor- gastrointestinal function is insufficient to en-
tality.63 The average intake was 1 to 2 packages sure adequate absorption of nutrients and flu-
per day, with 350 kcal and 20 g of protein plus ids.54-56,72 A central venous catheter is preferred
vitamin D and hydroxymethylbutyrate (HMB) for higher osmotic loads to prevent phlebitis and
contained in each package. Similar results were when parenteral nutrition is required for longer
also observed in a subgroup analysis of data than a few weeks. Central access carries the risk
from patients with COPD.65 Moreover, early nu- of bloodstream infection and thrombosis. For
tritional intake reduced complications and mor- long-term use, such as in patients with chronic
tality among patients hospitalized for acute heart intestinal failure, a central venous catheter is
failure.66 tunneled subcutaneously from the venous access
Systematic reviews and meta-analyses sup- point to the skin exit.
port the conclusions from these two trials.67-69 Parenteral solutions meet basic glucose needs,
The more recent and well-conducted studies ap- provide adequate energy, and provide amino ac-
pear to offer the best evidence.69 Questions for ids for protein synthesis. Approximately 125 g of
further investigation are whether some of the glucose per day is sufficient, but up to 200 g per
essential amino acids (e.g., leucine and HMB) day may be protein-sparing. At the beginning of
have specific anabolic effects and whether ma- nutritional treatment, a reduced dextrose load
rine n−3 fatty acids have immunomodulatory as can be administered to assess whether paren-
well as growth-promoting effects. teral nutrition is associated with unacceptable
side effects. Glucose monitoring is required to
Enteral Nutrition ensure appropriate insulin coverage. Essential
Enteral nutrition is provided with a tube inserted fatty acid requirements can be met with ap-
orally through a nostril into the stomach or proximately 200 g of lipid emulsion per week,
proximal small intestine (for use for up to a few but usually up to half the nonprotein energy is
weeks) or placed directly into the gastrointesti- provided by lipids. The first lipid emulsions were
nal tract as a nutritive stoma by means of percu- based on soybean oil, which is rich in n−6 fatty
taneous endoscopic gastrostomy or surgery.70 acids. In recent years, lipid preparations based
Patients who are conscious often find the dis- on monounsaturated oleic acid and n−3 polyun-
comfort associated with a nasogastric tube un- saturated fatty acids have been introduced, since
acceptable. Once the correct position of the tube high soybean oil concentrations may cause
has been confirmed, enteral nutrition is usually hepatobiliary complications. Moreover, a lower
administered in intermittent doses (boluses) of ratio of n−6 to n−3 polyunsaturated fatty acids
500 ml.71 Especially in acute care settings, con- may modulate the inflammatory response. Ami-
tinuous flow with pump control for 20 to 24 no acid solutions should provide 0.10 to 0.15 g
hours per day is an option. Conversion to post- of nitrogen per kilogram per day as a basal
pyloric feeding is recommended if gastric feed- replacement. In inflammatory and hypermeta-
ing is not acceptable to the patient.54 bolic states, 0.15 to 0.20 g of nitrogen per kilo-
A slow infusion rate at the beginning of gram per day is required. Fat- and water-soluble
therapy may prevent gastrointestinal and meta- vitamins and trace elements should be added to
bolic symptoms. If nausea and vomiting occur, complete parenteral nutrition.
feeding should be reduced or discontinued to Complications of parenteral nutrition include
lower the risk of pulmonary aspiration. Proki- mainly catheter-related thrombosis and blood-
netic medications may be considered. Diarrhea stream infections but also local infections at the
is the most common complication. Metabolic exit site. Metabolic complications are usually re-
complications of enteral nutrition include fluid lated to the rate of infusion. Elevated blood glucose
imbalances, hyperglycemia, electrolyte abnormal- levels, changes in blood electrolyte levels, azote-
ities, and occasionally, refeeding syndrome (dis- mia, and hypertriglyceridemia are common. He-
cussed below). patic dysfunction, often with cholestasis or hepatic

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 Malnutrition in Adults

steatosis, may complicate long-term parenteral Sum m a r y

nutrition. Maintaining some level of oral or en-
teral intake or using alternative lipid emulsions Malnutrition in adults follows two major patho-
is likely to reduce hepatobiliary risks. For pa- logical pathways — nutrient deprivation and in-
tients receiving enteral or parenteral nutrition at flammation-induced anorexia with tissue catabo-
home, outpatient nutritional counseling is criti- lism — and can be divided into disease-related
cal for clinical outcomes, including survival.73,74 malnutrition with inflammation, disease-related
malnutrition without perceived inflammation,
Refeeding Syndrome and non–disease-related malnutrition. Loss of
Refeeding syndrome may develop, especially in muscle mass and weakness contribute to sarcope-
severely malnourished patients, at the beginning nia and amplify frailty in older adults. Increased
of nutritional therapy.75 Cautious initial caloric susceptibility to infection and dysfunction of
and fluid provision and careful monitoring are major organ systems are the main negative con-
warranted to prevent this syndrome. sequences.
When supplied glucose increases insulin lev- Malnutrition occurs in up to 10% of commu-
els, phosphate, potassium, and magnesium shift nity-dwelling older people and in 20 to 50% of
intracellularly in the blood, and serum concen- hospitalized or institutionalized older people
trations are decreased. This shift can lead to and is an imminent threat for critically ill pa-
hypophosphatemia, edema, and cardiac and re- tients with a high inflammatory burden. Adults
spiratory failure (tachycardia and tachypnea, in admitted to hospitals or long-term care facilities
particular) and should be carefully monitored. should be screened for the risk of malnutrition,
Thiamine requirements increase during the and a diagnosis of malnutrition should be docu-
transition from starvation to feeding. Wernicke’s mented. The recently introduced GLIM approach,
encephalopathy, characterized by confusion, de- which includes weight loss, underweight, and
lirium, ataxia, and ophthalmoplegia, may occur. low muscle mass as phenotypic criteria and de-
Thiamine supplementation is generally given to creased food intake or assimilation and an in-
prevent this life-threatening complication. flammatory disease burden as etiologic criteria,
Treatment and prevention of refeeding syn- is promising for a future consensus approach to
drome consist of reducing caloric and fluid de- the diagnosis of malnutrition.
livery, correcting low blood levels of phosphate Persons with malnutrition should receive nu-
and other electrolytes and nutrients (thiamine), tritional counseling and oral, enteral, or paren-
and slowly increasing nutrients and fluids to teral nutrition as appropriate. Electrolyte, cardi-
recommended levels within 4 to 7 days.75 ac, and respiratory monitoring are essential for
preventing refeeding syndrome. Precision nutri-
Possible Future Developments tion will allow for personalized treatment. In
Pharmacologic treatments to improve appetite general, daily energy and protein requirements
(e.g., megestrol acetate and ghrelin agonists) or are 20 to 30 kcal per kilogram and 0.8 to 1.5 g
anabolism (e.g., myostatin decoy receptors and of protein per kilogram. In recent years, large-
selective androgen receptor modulators) have been scale randomized, controlled trials have shown
tested over the years, but without major break- the beneficial effects of individualized nutri-
throughs. Nevertheless, ongoing research is likely tional counseling combined with energy- and
to improve the understanding and treatment of protein-fortified oral nutritional supplements.
malnutrition. Examples of the topics of such re- Interventions may still not reverse the condition
search include interactions between the gut micro- because of the inflammatory nature of the un-
biome and malnutrition, genomic and metabolo- derlying disease. Future directions for research
mic profiling for precision nutritional treatments, include a refinement of the techniques for de-
the anorexia of aging and the potential develop- tecting malnutrition and a better understanding
ment of pharmacologic appetite stimulants, and of catabolic metabolism and anorectic mecha-
potential stroma-cell infusions. The development nisms, leading to improved treatment.
of options for treatment that are environmentally Disclosure forms provided by the authors are available with
sustainable is a contemporary challenge. the full text of this article at NEJM.org.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

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