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Protein-Energy Undernutrition (PEU)

By

Shilpa N Bhupathiraju

, PhD, Harvard Medical School and Brigham and Women's Hospital;


Frank Hu

, MD, MPH, PhD, Harvard T.H. Chan School of Public Health

Reviewed/Revised Oct 2023
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Topic Resources

Protein-energy undernutrition (PEU), previously called protein-energy malnutrition, is an energy deficit due to deficiency of all macronutrients, but primarily protein. It commonly includes deficiencies of many micronutrients. PEU can be sudden and total (starvation) or gradual. Severity ranges from subclinical deficiencies to obvious wasting (with edema, hair loss, and skin atrophy) to starvation. Multiple organ systems are often impaired. Diagnosis usually involves laboratory testing, including serum albumin. Treatment consists of correcting fluid and electrolyte deficits with IV solutions, then gradually replenishing nutrients, orally if possible.

In countries with sufficient food resources, PEU is common among institutionalized older patients (although often not suspected) and among patients with disorders that decrease appetite or impair nutrient digestion, absorption, or metabolism. In countries with high rates of food insecurity, PEU affects children who do not consume enough calories or protein.

Classification and Etiology of PEU

PEU is graded as mild, moderate, or severe. Grade is determined by calculating weight as a percentage of expected weight for length or height using international standards (normal, 90 to 110%; mild PEU, 85 to 90%; moderate, 75 to 85%; severe, < 75%).

PEU may be

  • Primary: Caused by inadequate nutrient intake

  • Secondary: Results from disorders or drugs that interfere with nutrient use

Primary PEU

In children, chronic primary PEU has 3 common forms:

  • Marasmus

  • Kwashiorkor

  • Marasmic kwashiorkor

The form depends on the balance of nonprotein and protein sources of energy. Starvation is an acute severe form of primary PEU.

Marasmus (also called the dry form of PEU) is a severe deficiency of calories and protein that tends to develop in infants and very young children. It causes weight loss and depletion of fat and muscle. In marasmus, most of the body's subcutaneous fat and deeper fat stores are lost, making the ribs, hips, facial bones, and spine visible through the skin. In countries with high rates of food insecurity, marasmus is the most common form of PEU in children.

Kwashiorkor (also called the wet, swollen, or edematous form) is a risk after premature abandonment of breastfeeding, which typically occurs when a younger sibling is born, displacing the older child from the breast. So children with kwashiorkor tend to be older than those with marasmus. Kwashiorkor may also result from an acute illness, often gastroenteritis Overview of Gastroenteritis Gastroenteritis is inflammation of the lining of the stomach and small and large intestines. Most cases are infectious, although gastroenteritis may occur after ingestion of drugs, medications... read more or another infection (probably secondary to cytokine release), in a child who already has PEU. A diet that is more deficient in protein than energy may be more likely to cause kwashiorkor than marasmus. Less common than marasmus, kwashiorkor tends to be confined to specific parts of the world, such as rural Africa, the Caribbean, and the Pacific islands. In these areas, staple foods (eg, yams, cassavas, sweet potatoes, green bananas) are low in protein and high in carbohydrates. Children with kwashiorkor have stunted growth; unnaturally blond, sparse, and brittle hair; and discolored patches of skin. In kwashiorkor, cell membranes leak, causing extravasation of intravascular fluid and protein, resulting in peripheral edema.

Marasmic kwashiorkor occurs when a child with kwashiorkor does not consume enough calories. It is characterized by features of marasmus and kwashiorkor—edema and wasting.

In both marasmus and kwashiorkor, cell-mediated immunity is impaired, increasing susceptibility to infections. Bacterial infections (eg, pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , gastroenteritis Overview of Gastroenteritis Gastroenteritis is inflammation of the lining of the stomach and small and large intestines. Most cases are infectious, although gastroenteritis may occur after ingestion of drugs, medications... read more , otitis media Otitis Media (Acute) Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. Symptoms include otalgia, often with systemic symptoms (eg, fever... read more Otitis Media (Acute) , urinary tract infections Bacterial Urinary Tract Infections Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more , sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more ) are common. Infections result in release of cytokines, which cause anorexia, worsen muscle wasting, and cause a marked decrease in serum albumin levels.

Starvation is a complete lack of nutrients. It occasionally occurs when food is available (as in fasting or anorexia nervosa) but usually occurs because food is unavailable (eg, during famine or wilderness exposure).

Secondary PEU

This type most commonly results from the following:

Pathophysiology of Protein-Energy Undernutrition

The initial metabolic response of PEU is decreased metabolic rate. To supply energy, the body first breaks down adipose tissue. However, later, when these tissues are depleted, the body may use protein for energy, resulting in a negative nitrogen balance. Visceral organs and muscle are broken down, resulting in a decrease in weight. Loss of organ weight is greatest in the liver and intestine, intermediate in the heart and kidneys, and least in the nervous system.

Symptoms and Signs of Protein-Energy Undernutrition

Symptoms of moderate PEU can be constitutional or involve specific organ systems. Apathy and irritability are common. The patient is weak, and work capacity decreases. Cognition and sometimes consciousness are impaired. Temporary lactose deficiency and achlorhydria develop. Diarrhea is common and can be aggravated by deficiency of intestinal disaccharidases, especially lactase Etiology . Gonadal tissues atrophy. PEU can cause amenorrhea in women and loss of libido in men and women.

Wasting of fat and muscle is common in all forms of PEU. If starvation is prolonged, weight loss may reach 50% in adults and possibly more in children.

In adults, cachexia is most obvious in areas where prominent fat depots normally exist (eg, ribs, hips, facial bones, spine). Muscles shrink and bones protrude. The skin becomes thin, dry, inelastic, pale, and cold. The hair is dry and falls out easily, becoming sparse. Wound healing is impaired. In older patients, risk of hip fractures and pressure (decubitus) ulcers increases.

With acute or chronic severe PEU, heart size and cardiac output decrease; pulse slows and blood pressure falls. Respiratory rate and vital capacity decrease. Body temperature falls, sometimes contributing to death. Edema, anemia, jaundice, and petechiae can develop. Liver, kidney, or heart failure may occur.

Marasmus in infants causes hunger, weight loss, growth retardation, and wasting of subcutaneous fat and muscle. Ribs and facial bones appear prominent. Loose, thin skin hangs in folds.

Kwashiorkor is characterized by peripheral and periorbital edema due to the decrease in serum albumin. The abdomen protrudes because abdominal muscles are weakened, the intestine is distended, the liver enlarges, and ascites Ascites Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more is present. The skin is dry, thin, and wrinkled; it can become hyperpigmented and fissured and later hypopigmented, friable, and atrophic. Skin in different areas of the body may be affected at different times. The hair can become thin, reddish brown, or gray. Scalp hair falls out easily, eventually becoming sparse, but eyelash hair may grow excessively. Alternating episodes of undernutrition and adequate nutrition may cause the hair to have a dramatic “striped flag” appearance. Affected children may be apathetic but become irritable when held.

Total starvation is fatal in 8 to 12 weeks. Thus, certain symptoms of PEU do not have time to develop.

Diagnosis of Protein-Energy Undernutrition

  • Diagnosis usually based on history

  • To determine severity: Body mass index (BMI), serum albumin, total lymphocyte count, CD4+ count, and serum transferrin

  • To diagnose complications and consequences: Complete blood count, electrolytes, blood urea nitrogen, glucose, calcium, magnesium, and phosphate

Physical examination may include measurement of height and weight, inspection of body fat distribution, and anthropometric measurements of lean body mass. Body mass index (BMI = weight[kg]/height[m]2) is calculated to determine severity. Findings can usually confirm the diagnosis.

Laboratory tests are required if dietary history does not clearly indicate inadequate caloric intake. Measurement of serum albumin, total lymphocyte count, CD4+ T lymphocytes, transferrin, and response to skin antigens may help determine the severity of PEU (see table ) or confirm the diagnosis in borderline cases. Many other test results may be abnormal: eg, decreased levels of hormones, vitamins, lipids, cholesterol, prealbumin, insulin-like growth factor-1, fibronectin, and retinol-binding protein. Urinary creatinine and methylhistidine levels can be used to gauge the degree of muscle wasting. Because protein catabolism slows, urinary urea level also decreases. These findings rarely affect treatment.

Table

Laboratory tests are required to identify causes of suspected secondary PEU. C-reactive protein or soluble interleukin-2 receptor should be measured when the cause of undernutrition is unclear; these measurements can help determine whether there is cytokine excess (possibly suggesting otherwise occult inflammatory or wasting disorders such as infection, hyperthyroidism, AIDS Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more Human Immunodeficiency Virus (HIV) Infection , or cancer). Thyroid function tests may also be done.

Other laboratory tests can detect associated abnormalities that may require treatment. Serum electrolytes, blood urea nitrogen, glucose, and possibly levels of calcium, magnesium, and phosphate should be measured. Levels of blood glucose, electrolytes (especially potassium, occasionally sodium), phosphate, calcium, and magnesium are usually low. Blood urea nitrogen is often low unless renal failure is present. Metabolic acidosis may be present. Complete blood count is usually obtained; normocytic anemia (usually due to protein deficiency) or microcytic anemia (due to simultaneous iron deficiency) is usually present.

Stool cultures should be obtained and checked for ova and parasites Diagnosis Human parasites are organisms that live on or in a person and derive nutrients from that person (its host). There are 3 types of parasites: Single-cell organisms (protozoa, microsporidia) Multicellular... read more if diarrhea is severe or does not resolve with treatment. Sometimes urinalysis, urine culture, blood cultures, tuberculin testing, and a chest x-ray are used to diagnose occult infections because people with PEU may have a muted response to infections.

Treatment of Protein-Energy Undernutrition

  • Usually oral feeding

  • Possibly avoidance of lactose (eg, if persistent diarrhea suggests lactose intolerance)

  • Supportive care (eg, environmental changes, assistance with feeding, orexigenic medications)

  • For children, feeding delayed 24 to 48 hours

Worldwide, the most important PEU preventive strategy is to reduce poverty and improve nutritional education and public health measures.

Mild or moderate PEU, including brief starvation, can be treated by providing a balanced diet, preferably orally. Liquid oral food supplements (usually lactose-free) can be used when solid food cannot be adequately ingested. Diarrhea often complicates oral feeding because starvation makes the gastrointestinal tract more likely to move bacteria into Peyer patches, facilitating infectious diarrhea. If diarrhea persists (suggesting lactose intolerance Carbohydrate Intolerance Carbohydrate intolerance is the inability to digest certain carbohydrates due to a lack of one or more intestinal enzymes. Symptoms include diarrhea, abdominal distention, and flatulence. Diagnosis... read more ), yogurt-based rather than milk-based formulas are given because people with lactose intolerance can tolerate yogurt. Patients should also be given a multivitamin supplement.

Other treatments may be needed to correct specific deficiencies, which may become evident as weight increases. To avoid deficiencies, patients should take micronutrients at about twice the recommended daily allowance until recovery is complete.

Children

Underlying disorders in children with PEU should be treated.

For children with diarrhea, feeding may be delayed 24 to 48 hours to avoid making the diarrhea worse; during this interval, children require oral or IV rehydration Oral Rehydration Oral fluid therapy is effective, safe, convenient, and inexpensive compared with IV therapy. Oral fluid therapy is recommended by the American Academy of Pediatrics and the World Health Organization... read more . Feedings are given often (6 to 12 times/day) but, to avoid overwhelming the limited intestinal absorptive capacity, are limited to small amounts (< 100 mL). During the first week, milk-based formulas with supplements added are usually given in progressively increasing amounts; after a week, the full amounts of 175 kcal/kg and 4 g of protein/kg can be given. Twice the recommended daily allowance of micronutrients should be given, using commercial multivitamin supplements. After 4 weeks, the formula can be replaced with whole milk plus cod liver oil and solid foods, including eggs, fruit, and meats.

Energy distribution among macronutrients should be about 16% protein, 50% fat, and 34% carbohydrate. An example is a combination of powdered cow’s skimmed milk (110 g), sucrose (100 g), vegetable oil (70 g), and water (900 mL). Many other formulas (eg, whole [full-fat] fresh milk plus corn oil and maltodextrin) can be used. Milk powders used in formulas are diluted with water.

Usually, supplements should be given with the formulas:

  • Magnesium 0.4 mEq/kg/day IM is given for 7 days.

  • B-complex vitamins at twice the recommended daily allowance are given parenterally for the first 3 days, usually with vitamin A, phosphorus, zinc, manganese, copper, iodine, fluoride, molybdenum, and selenium.

  • Because absorption of oral iron is poor in children with PEU, oral or IM iron supplementation may be necessary.

Parents are taught about nutritional requirements.

Adults

Underlying disorders should be treated. For example, if AIDS or cancer results in excess cytokine production, megestrol acetate or medroxyprogesterone may improve food intake. However, because these medications dramatically decrease testosterone in men (possibly causing muscle loss), testosterone should be replaced. Because these medications can cause adrenal insufficiency, they should be used only short-term (< 3 months).

An orexigenic medication, such as the cannabis extract dronabinol, should be given to patients with anorexia when no cause is obvious or to patients at the end of life when anorexia impairs quality of life. An anabolic steroid (eg, testosterone enanthate, nandrolone) or growth hormone can benefit patients with cachexia due to renal failure and possibly older patients (eg, by increasing lean body mass or possibly by improving function).

Correction of PEU in adults generally resembles that in children; feedings are often limited to small amounts. However, for most adults, feeding does not need to be delayed. A commercial formula for oral feeding can be used. Daily nutrient supply should be given at a rate of 60 kcal/kg and 1.2 to 2 g of protein/kg. If liquid oral supplements are used with solid food, they should be given at least 1 hour before meals so that the amount of food eaten at the meal is not reduced.

Treatment of institutionalized older patients with PEU requires multiple interventions:

  • Environmental measures (eg, making the dining area more attractive)

  • Feeding assistance

  • Changes in diet (eg, use of food enhancers and caloric supplements between meals)

  • Treatment of depression and other underlying disorders

  • Use of orexigenic medications, anabolic steroids, or both

The long-term use of gastrostomy tube feeding is essential for patients with severe dysphagia Dysphagia Dysphagia is difficulty swallowing. The condition results from impeded transport of liquids, solids, or both from the pharynx to the stomach. Dysphagia should not be confused with globus sensation... read more ; its use in patients with dementia is controversial. Increasing evidence supports the avoidance of unpalatable therapeutic diets (eg, low salt, diabetic, low cholesterol) in institutionalized patients because these diets decrease food intake and may cause severe PEU.

In patients with functional limitations, home delivery of meals and feeding assistance are key.

Complications of treatment

Treatment of PEU can cause complications (refeeding syndrome), including fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea. Diarrhea is usually mild and resolves; however, diarrhea in patients with severe PEU occasionally causes severe dehydration or death. Causes of diarrhea (eg, sorbitol used in elixir tube feedings, Clostridioides difficile if the patient has received an antibiotic) may be correctable. Osmotic diarrhea due to excess calories is rare in adults and should be considered only when other causes have been excluded.

Because PEU can impair cardiac and renal function, overhydration Volume Overload Volume overload generally refers to expansion of the extracellular fluid (ECF) volume. ECF volume expansion typically occurs in heart failure, kidney failure, nephrotic syndrome, and cirrhosis... read more can cause intravascular volume overload. Treatment decreases extracellular potassium and magnesium. Depletion of potassium or magnesium may cause arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more Overview of Arrhythmias . Carbohydrate metabolism that occurs during treatment stimulates insulin release, which drives phosphate into cells. Hypophosphatemia Hypophosphatemia Hypophosphatemia is a serum phosphate concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcohol use disorder, burns, starvation, and diuretic use. Clinical features include muscle weakness... read more can cause muscle weakness, paresthesias, seizures, coma, and arrhythmias. Because phosphate levels can change rapidly during parenteral feeding, levels should be measured regularly.

During treatment, endogenous insulin may become ineffective, leading to hyperglycemia. Dehydration and hyperosmolarity can result. Fatal ventricular arrhythmias can develop, possibly caused by a prolonged QT interval.

With parenteral feedings, infection is a risk because the catheter is left in place for a long time and the glucose in the solution promotes bacterial growth.

For unknown reasons, total parenteral nutrition Total Parenteral Nutrition (TPN) Parenteral nutrition is by definition given IV. Partial parenteral nutrition supplies only part of daily nutritional requirements, supplementing oral intake. Many hospitalized patients are given... read more , when given for more than about 3 months, causes bone density to decrease in some people. The best treatment is to temporarily or permanently stop this type of feeding. Total parenteral nutrition can also cause liver malfunction, most commonly in premature infants. Blood tests are done to monitor liver function. Adjusting the solution may help. Gallstones Choledocholithiasis and Cholangitis Choledocholithiasis is the presence of stones in bile ducts; the stones can form in the gallbladder or in the ducts themselves. These stones cause biliary colic, biliary obstruction, gallstone... read more may develop. Treatment involves adjusting the solution and, if possible, providing food orally or by feeding tube.

A feeding tube may irritate and erode nasopharyngeal and/or esophageal tissues. In such cases, using a different type of feeding tube may enable feedings to continue. In older patients fed by tube, aspiration is common. Food is less likely to be aspirated when the solution is given slowly and when the head of the bed is elevated for 1 to 2 hours after tube feeding.

Prognosis for Protein-Energy Undernutrition

Children

In children, mortality varies from 5 to 40%. Mortality rates are lower in children with mild PEU and those given intensive care. Death in the first days of treatment is usually due to electrolyte deficits, sepsis, hypothermia, or heart failure. Impaired consciousness, jaundice, petechiae, hyponatremia, and persistent diarrhea are ominous signs. Resolution of apathy, edema, and anorexia is a favorable sign. Recovery is more rapid in kwashiorkor than in marasmus.

Long-term effects of PEU in children are not fully documented. Some children develop chronic malabsorption and pancreatic insufficiency. In very young children, mild intellectual disability may develop and persist until at least school age. Permanent cognitive impairment may occur, depending on the duration, severity, and age at onset of PEU.

Adults

In adults, PEU can result in morbidity and mortality (eg, progressive weight loss increases mortality rate for older patients in nursing homes). In older patients, PEU increases the risk of morbidity and mortality due to surgery, infections, or other disorders.

Except when organ failure occurs, treatment is uniformly successful.

Key Points

  • PEU can be primary (ie, caused by decreased intake of nutrients) or secondary to gastrointestinal disorders, wasting disorders, or conditions that increase metabolic demand.

  • In severe forms of PEU, body fat and eventually visceral tissue are lost, immunity is impaired, and organ function slows, sometimes resulting in multiple organ failure.

  • To determine severity, measure body mass index (BMI), serum albumin, total lymphocyte count, CD4 count, and serum transferrin.

  • To diagnose complications and consequences, measure complete blood count, electrolytes, blood urea nitrogen, glucose, calcium, magnesium, and phosphate.

  • For mild PEU, recommend a balanced diet, sometimes avoiding foods that contain lactose.

  • For severe PEU, hospitalize patients, give them a controlled diet, correct fluid and electrolyte abnormalities, and treat infections; common complications of treatment (refeeding syndrome) include fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea.

Drugs Mentioned In This Article

Drug Name Select Trade
Colief, Lac-Dose , Lactaid, Lactaid Fast Act, Lactrase
Cod Liver Oil, Cod Liver Oil Double Strength
A Mulsin, A-Caro-25, Aquasol A, Dofsol-A
Megace, Megace ES
Amen, Depo-Provera, Depo-subQ Provera 104, Provera
Marinol, SYNDROS
Androderm, AndroGel, Andro-L.A., Aveed, AXIRON, Delatestryl, Depo-Testosterone, FORTESTA, JATENZO, KYZATREX, Natesto, STRIANT, Testim, Testoderm, Testone CIK, Testopel, TLANDO, Virilon, Vogelxo, XYOSTED
Numoisyn, Saliva Substitute
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