Pharmacotherapy A Pathophysiologic Approach, 9th Ed.

118. Assessment of Nutrition Status and Nutrition Requirements

Katherine Hammond Chessman and Vanessa J. Kumpf


 Images Malnutrition is a consequence of nutrient imbalance, overnutrition or undernutrition, and has a high prevalence in the United States.

 Images Nutrition screening is distinct from assessment and should be designed to quickly and reliably identify those who are at risk of nutrition-related poor outcomes.

 Images A comprehensive nutrition assessment is the first step in formulating a nutrition care plan for a patient who is found to be nutritionally at risk.

 Images A nutrition-focused medical, surgical, and dietary history and a nutrition-focused physical examination are key components of a comprehensive nutrition assessment.

 Images Appropriate evaluation of anthropometric measurements (e.g., weight, height) is essential in nutrition assessment and should be based on published standards.

 Images Laboratory assessment of visceral proteins is essential for a comprehensive nutrition assessment and must be interpreted in the context of physical findings, medical and surgical history, and the patient’s clinical status.

 Images The presence of micronutrient or macronutrient deficiencies or risk factors for these deficiencies can be identified by a comprehensive nutrition assessment.

 Images Patient-specific goals should be established using evidence-based criteria considering the patient’s clinical condition and the need for maintenance or repletion in adults or continued growth and development in children.

 Images Indirect calorimetry is the most accurate method to determine energy requirements, but because of cost and availability, validated predictive equations are most often used to determine energy requirements.

 Images Drug–nutrient interactions can affect nutrition status and the response to and adverse effects seen with drug therapy and must be considered when developing or assessing a patient’s nutrition care plan.


Nutrition is a vital component of quality patient care. No single clinical or laboratory parameter is an absolute indicator of nutrition status, so data from a number of areas must be analyzed. This chapter reviews the tools most commonly used for accurate, relevant, and cost-effective nutrition screening and assessment. The various methods used to determine patient-specific macro-and micronutrient requirements and potential drug–nutrient interactions are also discussed.


Images Malnutrition is a consequence of nutrient imbalance. In general, deficiency states can be categorized as those involving protein and calories or single nutrients such as individual vitamins or trace elements. Starvation-associated malnutrition, marasmus, results from prolonged inadequate intake, absorption, or utilization of protein and energy. It occurs in patients with an inadequate food supply, anorexia nervosa, major depression, and malabsorption syndromes. Somatic protein (skeletal muscle) and adipose tissue (subcutaneous fat) wasting occurs, but visceral protein (e.g., albumin [ALB] and transferrin [TFN]) production is usually preserved. Weight loss may exceed 10% of usual body weight (UBW; typical weight). With severe marasmus, cell-mediated immunity and muscle function are impaired. Patients with marasmus commonly have a prototypical starved, wasted appearance.1,2 Kwashiorkor is a specific form of starvation-associated malnutrition that develops when there is inadequate protein intake and usually develops in areas where there is famine, limited food supply, or low educational levels. Although rarely reported in the United States, children who are abused or neglected and elderly individuals can develop this condition. Often patients with kwashiorkor do not appear malnourished because of relative adipose tissue sparing, especially with mild undernutrition, but visceral (and to some degree somatic) protein stores are depleted, resulting in severe hypoalbuminemia and edema in more advanced cases. In patients with marasmus or kwashiorkor, enhancing nutritional intake or bypassing impaired absorption with specialized nutrition support can reverse the malnutrition.1,2

Malnutrition can also result from chronic mild-to-moderate inflammation when there is heightened cellular substrate demand or use, such as in patients with chronic inflammatory diseases, organ failure, or cancer. In patients with severe acute disease or injury (e.g., major infections, burns, trauma, traumatic brain injury), malnutrition can develop because of increased metabolic demands. Individuals with mild-to-moderate marasmus or kwashiorkor can develop marked malnutrition when severe injury or inflammation occurs. In patients with inflammation or injury-associated malnutrition, simply providing nutrients in usual or even increased amounts may not be sufficient to reverse the nutrient imbalance caused by hypermetabolism. Regardless of the cause, undernutrition can result in changes in subcellular, cellular, or organ function that increase the individual’s risks of morbidity and mortality.

Obesity (overnutrition) is a major healthcare concern worldwide. In 2009 to 2010, approximately 69% of American adults were overweight (defined as a body mass index [BMI] ≥25 kg/m2), and about 36% (78 million) were obese (BMI ≥30 kg/m2).3 In 2010, obesity prevalence ranged from 21% in Colorado to 34% in Mississippi.4 Additionally, 17% (12.5 million) of all U.S. children and adolescents (age 2–19 years) were obese (BMI ≥95th percentile for age on the gender-appropriate BMI-for-age Centers for Disease Control and Prevention’s [CDC’s] 2000 growth chart).5,6 Many more children (∼32%) were overweight (BMI ≥85th percentile for age).5 Although the Healthy People 2010 goals of 15% obesity in adults and 5% obesity in children7 were not met, there was no change in obesity prevalence among U.S. adults or children in 2009 to 2010 compared with 2003 to 20083 or 2007 to 2008,5respectively. This leveling trend is encouraging after a steady increase in prevalence since 1999. Nutrition assessment allows identification of overweight and obese individuals and those at risk of becoming obese. The consequences of obesity are numerous and include type 2 diabetes mellitus, cardiovascular disease, and stroke.

Poor nutritional status is associated with higher morbidity and mortality in many settings. An effective nutrition screening program will identify patients at nutrition-related risk. Clinicians trained to perform a comprehensive nutrition assessment will accurately characterize the at-risk patient’s baseline nutrition status, allowing an appropriate estimate of an individual’s nutrition needs and development of a patient-specific nutrition care plan. Diligent monitoring of ongoing nutrition status will ensure that nutrition-related goals are being met and patient outcomes are improved.


Images Nutrition screening is distinct from nutrition assessment.8,9 It is neither practical nor warranted to conduct a comprehensive nutrition assessment on every individual; thus, nutrition screening protocols are useful to provide a reliable, systematic method to identify persons for whom a detailed nutrition assessment is needed. A nutrition screen can be used to detect those who are overweight, obese, malnourished, or at risk for malnutrition; predict the probability of their outcome as a result of nutritional factors; and identify those who would benefit from nutritional treatment. Ideally, potential nutrition-related issues can be identified and addressed before complications develop.

The ideal nutrition screen is quick, simple, and noninvasive and can be done by lay and healthcare providers in many settings, including homes, long-term care facilities, ambulatory care clinics, and hospitals. The Joint Commission includes nutrition screening and assessment in its performance standards for accredited healthcare institutions.10 Each entity must have a written process by which a nutrition screen is done and criteria that determine when a more in-depth assessment will be performed. In hospitals, a nutrition screen must be completed within 24 hours of admission. A comprehensive nutrition assessment, if needed, should be completed within 48 to 72 hours. For outpatients, nutrition screening should occur ideally at the first visit with a new provider and thereafter as warranted by the patient’s condition. Nutrition screening is a cost-effective way to decrease complications and length of hospital stay.

Appropriate screening is based on risk factor identification. Risk factors for undernutrition include recent weight loss, presence of chronic disease states, disease severity, complicating conditions, treatments, and socioeconomic factors that may result in a decreased nutrient intake or altered nutrient metabolism, utilization, or malabsorption. Risk factors for obesity include BMI, family history of obesity, certain medical diagnoses, poor dietary habits, lack of exercise, and some drug therapies. Various rating and classification systems have been proposed to screen for nutrition risk and guide subsequent interventions.8,1114 Checklists are used to quantify a person’s food and alcohol consumption habits; ability to buy, prepare, and eat food; weight history; diagnoses; and medical and surgical procedures. Nutrition screens for children most often evaluate growth parameters against the CDC or World Health Organization (WHO) growth charts6,15 and medical conditions known to increase nutrition risk. Screening programs should also identify patients receiving specialized nutrition support (enteral or parenteral nutrition). In any setting, patients determined to be “at nutrition risk” should receive a timely comprehensive nutrition assessment by a trained nutrition professional to verify nutrition-related risk and to formulate a nutrition care plan.


Images A comprehensive nutrition assessment is the first step in formulating a patient-specific nutrition care plan. Nutrition assessment has four major goals: (a) identification of the presence of factors associated with an increased risk of developing malnutrition, including disorders resulting from macro- or micronutrient deficiencies (undernutrition), obesity (overnutrition), or impaired nutrient metabolism or utilization; (b) determination of the risk of malnutrition-associated complications; (c) estimation of nutrition needs; and (d) establishment of baseline nutrition status with parameters against which to measure nutrition therapy outcomes. Nutrition assessment should include a nutrition-focused medical, surgical, and dietary history; a nutrition-focused physical examination, including anthropometrics; and laboratory measurements. A comprehensive nutrition assessment provides a basis for determining the patient’s nutrition requirements and the optimal type and timing of nutrition intervention.

Nutrition-Focused History and Physical Examination

Images The nutrition-focused medical, surgical, and dietary history provides information regarding factors that predispose to malnutrition (e.g., prematurity, chronic diseases, gastrointestinal [GI] dysfunction, alcohol abuse, acute or chronic inflammation, cancer, surgery, trauma), and overnutrition (e.g., poor dietary habits, limited exercise, chronic diseases, family history). The clinician should direct the interview to elicit any history of weight gain or loss, anorexia, vomiting, diarrhea, and decreased or unusual food intake (Table 118-1).

TABLE 118-1 Pertinent Data from a Nutrition-Focused Medical, Surgical, and Dietary History


The nutrition-focused physical examination takes a systems approach to assess lean body mass (LBM) and findings of deficiencies or excesses of vitamins, trace elements, or essential fatty acids. The degree of muscle wasting, edema, or loss of subcutaneous fat, if present, should be documented. The presence of findings suggestive of malnutrition (e.g., dermatitis, glossitis, cheilosis, jaundice) should be noted. Additionally, nonspecific indicators of ongoing inflammation or stress (e.g., fever, tachycardia) should be noted because these are important findings (Table 118-2).

TABLE 118-2 Physical Examination Findings Suggestive of Malnutrition


The Subjective Global Assessment, a simple, reproducible, cost-effective, bedside approach to nutrition assessment, has been used in a variety of patient populations.2,12,16,17 Five aspects of the medical and dietary history comprise the Subjective Global Assessment: weight changes in the previous 6 months, dietary changes, GI symptoms, functional capacity, and the presence of disease states known to affect nutrition status. Weight loss of less than 5% of UBW is considered a “small” loss, 5% to 10% loss is “potentially significant,” and more than a 10% loss is “definitely significant.” Dietary intake is characterized as normal or abnormal, and the duration and degree of abnormal intake are noted. The presence of daily GI symptoms (e.g., anorexia, nausea, vomiting, diarrhea) for longer than 2 weeks is significant. Functional capacity assesses the patient’s energy level and whether the patient is active or bedridden. Finally, disease states are assessed as to their impact on metabolic demands (i.e., no, low, moderate, or high stress). Four physical examination findings are rated as normal, mild, moderate, or severe: loss of subcutaneous fat (triceps and chest), muscle wasting (quadriceps and deltoids), edema (ankle and sacral), and ascites. The patient’s nutrition status is then rated as adequately nourished, moderately malnourished or suspected of being malnourished, or severely malnourished. Critics of the Subjective Global Assessment find it time-consuming and complex.2 Another tool, the Mini Nutritional Assessment, has been used extensively in geriatric patients and found to be useful for elderly living in the community, subacute care facilities, and nursing homes.2,18

Anthropometric Measurements

Images Anthropometric measurements, which are physical measurements of the size, weight, and proportions of the human body, are also used to assess nutrition status. Common measurements are weight, stature (standing height or recumbent length depending on age), head circumference (for children younger than 3 years of age), and waist circumference. Measurements of limb size, such as skinfold thickness, midarm muscle circumference, and wrist circumference, may be useful in selected individuals. Bioelectrical impedance analysis (BIA) is also an anthropometric assessment tool. An individual’s body measurements can be compared with normative population standards or repeated at various intervals to monitor response to a nutrition care plan. In adults, nutrition-related changes in anthropometric measurements occur slowly; several weeks or more are usually required before detectable changes are noted. In infants and young children, changes may occur more quickly. Acute changes in weight and skinfold thickness usually reflect changes in hydration, which must be considered when interpreting these parameters, particularly in hospitalized patients.

Weight, Stature, and Head Circumference

Body weight is a nonspecific measure of body cell mass, representing skeletal mass, body fat, and the energy-using component (i.e., LBM). Change in weight over time, particularly in the absence of edema, ascites, or voluntary losses, is an important indicator of altered LBM. Actual body weight (ABW) interpretation should include consideration of ideal weight for height, referred to as ideal body weight (IBW), UBW, fluid status, and age (Table 118-3). The UBW describes an individual’s typical weight. Dehydration will result in decreased ABW but not a loss in LBM. After the patient is rehydrated, rechecking the weight is important to establish a baseline to use for nutrition evaluation. Edema and ascites increase total body water (TBW), thereby increasing ABW. Thus, the ABW of patients with severe edema and ascites should not be used for nutrition assessment; practitioners often use a “dry weight” to account for this increase in TBW. Both acute and chronic changes in fluid status can affect the ABW; these changes often can be detected by monitoring the patient’s daily fluid intake and output. Accurate weight measurement can be difficult in critically ill patients because of their clinical condition and stress-related water retention.

TABLE 118-3 Evaluation of Body Weight


The IBW provides one population reference standard against which the ABW can be compared to detect both over- and undernutrition states. Numerous IBW-for-height reference tables have been generated. In clinical practice, mathematical equations based on gender and height (e.g., Hamwi method) are used commonly. IBW is calculated as 48 kg + (2.7 × [inches over 5 feet]) or 48 kg + (1.06 × [cm over 152 cm]) for adult men and for adult women as 45 kg + (2.3 × [inches over 5 feet]) or 45 kg + (0.906 × [cm over 152 cm]). For both equations, a range of ± 4.5 kg for large or small frame size is used for interpretation purposes. For obese adults, use of an adjusted ABW has been recommended for nutrition-related calculations, where adjusted ABW = ([ABW – IBW] × 0.25) + IBW. However, the use of this adjusted ABW is not evidence-based because most of the metabolic rate equations were developed with a mix of obese and nonobese individuals, and ABW was used to formulate the equations.19 The IBW of a child can be calculated as ([height in cm]2 × 1.65)/1,000. Alternatively, IBW for height can be determined by identifying the body weight corresponding to the same growth channel as the child’s measured stature on the appropriate CDC or WHO growth chart. Comparison with the 50th percentile weight-for-age has been suggested but can be misleading if the child’s height is not also at the 50th percentile.

Change in weight over time can be calculated as the percentage of UBW, where percent UBW = (ABW/UBW) × 100 (Table 118-3). Use of UBW as a reference point provides a more accurate reflection of clinically significant weight changes over time. However, determining UBW depends on patient or family recall, which may be inaccurate. The use of UBW avoids the problems associated with normative tables and documents comparative changes in body weight. Weight changes should be interpreted relative to time. Unintentional weight loss, especially rapid weight loss (i.e., 5% of UBW in 1 month or 10% of UBW in 6 months), increases the risk of poor clinical outcomes.12

Stature is determined by both genetics and nutrition. In infants, recumbent length is measured; in older children and adults, a standing height is preferred. If a standing height cannot be measured, the measurement of demispan can be used to estimate height. Demispan is determined in a seated patient by measuring the distance from the sternal notch to the web between the middle and ring fingers along a horizontally outstretched arm with the wrist in neutral rotation and zero extension or flexion. Demispan may more accurately assess stature in elderly adults, especially those with kyphosis or vertebral collapse. After the demispan is measured, height is estimated using the following equations: women: height (cm) = 1.35 × demispan (cm) + 60.1; men: height (cm) = 1.4 × demispan (cm) + 57.8.20 Knee height may also be used to estimate stature and is especially helpful in patients with limb contractures, such as patients with cerebral palsy.2023 Knee height is measured from just under the heel to the anterior surface of the thigh just proximal to the patella. Using the average of two measurements rounded to the nearest 0.1 cm, height can be estimated using the following equations: women: height (cm) = 84.88 (0.24 × age [years]) + (1.83 × knee height [cm]); men: height (cm) = 64.19 (0.04 × age [years]) + (2.02 × knee height [cm]).23

The best indicator of adequate nutrition in a child is appropriate growth. At each medical encounter, weight, stature, head circumference (until 3 years), and BMI (after 2 years) should be plotted on the WHO (younger than 2 years) or CDC gender- and age-specific growth curves. Specialized charts are available for assessment of short- and long-term growth of premature infants,24,25 children with Down’s syndrome,26 and children with other specific conditions. For premature infants with corrected postnatal age of 40 weeks or more, the WHO growth charts can be used; however, weight-for-age and length-for-age should be plotted according to corrected postnatal age until 2 years and 3.5 years of age, respectively.

Recommended intervals between measurements in young children are weight, 7 days; length, 4 weeks; height, 8 weeks; and head circumference, 7 days in infants and 4 weeks in children until 3 years of age. Growth velocity can be used to assess growth at intervals too close to plot accurately on a growth chart (Table 118-4). In newborns, average weight gain is 10 to 20 g/kg/day (24–35 g/day in term infants and 10–25 g/day in preterm infants). The rate of weight gain declines considerably after 3 months of age. Head growth (measured by head circumference), usually 0.5 cm/week (0.2 inches/week) during the first year of life, can be compromised during periods of critical illness or malnutrition. Rapid head growth, especially at a rate faster than expected, suggests hydrocephalus and should be further evaluated.

TABLE 118-4 Expected Growth Velocities in Term Infants and Children


Failure to thrive (growth failure) is defined as weight-for-age or weight-for-height (or length) below the 5th percentile or a falloff of two or more major percentiles (major percentiles are defined as 97th, 95th, 90th, 75th, 50th, 25th, 10th, 5th, and 3rd). Weight-for-height evaluation is age independent and helps differentiate a stunted child (chronic malnutrition) from a wasted child (acute malnutrition). Short stature, which can be associated with chronic disease, is a manifestation of chronic undernutrition. Short stature in the absence of poor weight gain suggests another etiology, such as growth hormone deficiency or constitutional growth delay.

Body Mass Index

Body mass index can be calculated as either body weight in kilograms divided by the patient’s height in meters squared (kg/m2) or body weight in pounds multiplied by 703 divided by the patient’s height in inches squared (lb/in2). A BMI of 25 kg/m2 or higher is considered a risk factor for premature death and disability. Health risks increase as the BMI increases. Although BMI correlates strongly with total body fat, individual variation, especially in very muscular persons, may lead to erroneous classification of nutrition status. BMI should be interpreted based on characteristics such as gender, frame size, and age. For example, at the same BMI, a woman tends to have more body fat than a man, and an older adult would have more body fat than a younger one.

In general, a BMI between 18.5 and 24.9 kg/m2 is indicative of a healthy weight, between 25 kg/m2 and 29.9 kg/m2 signifies being overweight, and 30 kg/m2 or higher indicates obesity (Table 118-3).12,27These BMI classifications may not be appropriate for older subjects, especially those older than 60 years, where a BMI between 27 kg/m2 and 30 kg/m2 has not been associated with the same increased nutrition-related risks seen in younger individuals.28 BMI has also been used to assess undernutrition (<18.5 kg/m2 indicates undernutrition), but this relationship is not as well established.12 Children 2 years of age and older are considered overweight if their BMI is at or above the 85th percentile on the age- and gender-specific CDC BMI chart and obese if the BMI is at or above the 95th percentile.6 Use of these charts at each medical encounter helps to heighten awareness of children whose BMI and family history put them at risk for adult obesity and its associated complications.

Clinical Controversy…

Clinicians often debate whether nutrition needs for overweight and obese patients should be calculated using IBW, ABW, or adjusted ABW.

Skinfold Thickness and Mid-Arm Muscle Circumference

More than 50% of the body’s fat is subcutaneous; thus, changes in subcutaneous fat reflect changes in total body fat. Whereas skinfold thickness measurement provides an estimate of subcutaneous fat, mid-arm muscle circumference, which is calculated using the skinfold thickness and mid-arm circumference, estimates skeletal muscle mass. Although simple and noninvasive, these anthropometric measurements are not used commonly in clinical practice but can be used for both population analysis and long-term monitoring of individuals. Triceps skinfold thickness is used most commonly, but reference standards also exist for subscapular and iliac sites. Careful technique in the use of pressure-regulated calipers is essential for reproducibility and reliability in measuring triceps skinfold thickness. Results should be interpreted cautiously because standards do not account for variation in bone size, muscle mass, hydration, or skin compressibility, and they do not consider obesity, ethnicity, illness, and increased age. Furthermore, these parameters change slowly in adults, often requiring weeks before significant alterations from baseline can be detected.

Waist Circumference

Waist circumference is a simple measurement used to assess abdominal (visceral) fat. Excess abdominal fat, rather than excess peripheral (subcutaneous) fat, is an independent predictor of obesity-related complications, especially diabetes mellitus and cardiovascular disease.29,30 Waist circumference is determined by measuring the distance around the smallest area below the rib cage and the top of the iliac crest. Men are at increased risk (beyond the BMI-related risk) if the waist circumference is greater than 40 inches (102 cm); women are at increased risk if the waist circumference is greater than 35 inches (89 cm); and children are at risk if the waist circumference is at the 75th percentile or greater (16–17-year-old girls) or 90th percentile (all others) according to age- and gender-specific standards.31

Waist-to-Hip and Waist-to-Height Ratios

Extra weight around the waist confers a greater health risk than extra weight around the hips and thighs. The waist-to-hip ratio is determined by dividing the waist circumference by the hip circumference (maximal posterior extension of the buttocks). In adults, a waist-to-hip ratio of greater than 0.9 in men and 0.85 in women is considered an independent risk factor for adverse health consequences.29 Waist-to-height ratio (both measured in centimeters) has been used to evaluate children at risk for the metabolic syndrome because, unlike waist circumference, it is independent of age and gender. A child with a waist-to-height ratio of more than 0.5 is at risk for developing the metabolic syndrome.32

Bioelectrical Impedance

Bioelectrical impedance is a simple, noninvasive, portable, and relatively inexpensive technique used to measure body composition.33,34 The technology is based on the fact that lean tissue has a higher electrical conductivity (less resistance) than fat, which is a poor current conductor because of its lower water and electrolyte content. When a small electric current is applied to two appendages (wrist and ankle or both feet), impedance (resistance) to flow is measured. Assessment of LBM, TBW, and water distribution can be determined with BIA. Increased TBW decreases impedance; thus, it is important to evaluate hydration along with BIA. Other potential limitations of BIA include variability with electrolyte imbalance and interference by large fat masses, environment, ethnicity, menstrual cycle phase, and underlying medical conditions. Although BIA equations have high validity when used in the population in which they were developed (mostly young healthy adults), BIA calculations are subject to considerable errors if applied to other populations. Although BIA measures body fat accurately in controlled trials, accuracy in clinical practice is inconsistent. The lack of reference standards that reflect variations in individual body size and clinical condition also limits BIA use in clinical practice. BIA is not superior to BMI as a predictor of overall adiposity in the general population and is currently used primarily as a research tool.


Diminished skeletal muscle function can be a useful indicator of malnutrition because muscle function is an end-organ response. Muscle function also recovers more rapidly in response to initiation of nutrition support than anthropometric measurements. Hand-grip strength (forearm muscle dynamometry), respiratory muscle strength, and muscle response to electrical stimulation have been used. Measuring hand-grip strength is a relatively simple, noninvasive, and inexpensive procedure that correlates with patient outcome.3537 Normative standards supplied by the manufacturer of the measuring device can be used to establish the presence of a deficiency state. Ulnar nerve stimulation causes measurable muscle contraction and is used in most intensive care units to monitor neuromuscular blockade. In malnourished patients, increased fatigue and a slowed muscle relaxation rate are noted; these indices return to normal with refeeding.

A number of methods have been used to determine body composition in the research setting, including bioimpedance spectroscopy, dual energy x-ray absorptiometry (DXA), quantitative CT, air displacement plethysmography, three-dimensional photonic scanning, MRI, quantitative MRI, and positron emission tomography.38,39 These methods are generally complex and require expensive technology. DXA, best known for its use in measuring bone density in patients with osteoporosis, is one of the most promising methods for routine clinical practice. It can be used to quantify the mineral, fat, and LBM compartments of the body and is available in most hospitals and many outpatient facilities. Equipment for a central DXA scan requires a fair amount of space, and the cost depends on the complexity of the scanner. Portable (or peripheral) DXA devices that use ultrasound and infrared interactance can be used to measure bone density in peripheral bones, such as the wrist, fingers, or heel, and have also been used to assess subcutaneous fat. These portable DXA scanners are much less expensive and can be used in community screenings in malls, health fairs, and pharmacies. Further research is needed to determine if DXA will be useful clinically in nutrition assessment. MRI and CT can measure subcutaneous, intraabdominal, and regional fat distribution and thus have the potential to be useful clinical tools.

Laboratory Assessment

Images Biochemically, LBM can be assessed by measuring the serum visceral proteins, albumin (ALB), transferrin (TFN), and prealbumin (also known as transthyretin). C-reactive protein (CRP) is useful as a marker of inflammation. Creatinine-height index has historically been calculated to assess LBM but is seldom done today because of the lack of evidence to support its usefulness.

Visceral Proteins

Measurement of serum proteins synthesized by the liver can be used to assess the visceral protein compartment. It is assumed that in undernutrition states, a low serum protein concentration reflects diminished hepatic protein synthetic mass and indirectly reflects the functional protein mass of other organs (heart, lung, kidney, intestines). Visceral proteins with the greatest relevance for nutrition assessment are serum ALB, TFN, and prealbumin. Many factors other than nutrition affect the serum concentration of these proteins, including age, abnormal kidney (nephrotic syndrome), GI tract (protein-losing enteropathy) or skin (burns) losses, hydration (dehydration results in hemoconcentration, overhydration in hemodilution), liver function (the synthetic site), and metabolic stress and inflammation (e.g., sepsis, trauma, surgery, infection). Assessing visceral proteins is of greatest value in the presence of uncomplicated semi-starvation and recovery. Thus, visceral protein concentrations must be interpreted relative to the individual’s overall clinical condition (Table 118-5). During severe acute stress (trauma, burns, sepsis), these proteins are relatively poor markers of nutrition status because of increased vascular permeability with dramatic fluid shifts and reprioritizing of liver protein synthesis increasing the production of acute-phase reactants such as CRP, ferritin, fibrinogen, and haptoglobin.40 CRP can be used in these cases to assess the degree of inflammation present: if CRP is elevated and ALB and prealbumin are decreased, then inflammation is a likely contributing factor. Assessing trends is most useful in these cases.

TABLE 118-5 Visceral Proteins Used for Assessment of Lean Body Mass


Albumin is the most abundant plasma protein and is involved in maintenance of colloid oncotic pressure and binding and transport of numerous hormones, anions, drugs, and fatty acids. It is widely used as a marker of chronic malnutrition. It is, however, a relatively insensitive index of early protein malnutrition because there is a large amount normally in the body (4–5 g/kg of body weight), it is extensively distributed in the extravascular compartment (60%), and it has a long half-life (18–20 days). However, chronic protein deficiency in the setting of adequate nonprotein calorie intake leads to marked hypoalbuminemia because of a net ALB loss from the intravascular and extravascular compartments. Serum ALB concentrations also are affected by moderate-to-severe calorie deficiency and liver, kidney, and GI disease. ALB is an acute-phase reactant, and serum concentrations decrease with inflammation, infection, trauma, stress, and burns. Decreased serum ALB concentrations are associated with poorer clinical outcomes in most of the above-mentioned settings. Additionally, serum ALB concentrations less than 2.5 g/dL (25 g/L) can be expected to exacerbate ascites and peripheral, pulmonary, and GI mucosal edema as a result of decreased colloid oncotic pressure. Hypoalbuminemia will also affect the interpretation of serum calcium concentrations as well as serum concentrations of highly protein bound drugs (e.g., phenytoin, valproic acid).

Transferrin is a glycoprotein that binds and transports ferric iron to the liver and reticuloendothelial system for storage. Because it has a shorter half-life (8–9 days) and there is less of it in the body (<100 mg/kg of body weight), TFN will decrease in response to protein and energy depletion before the serum ALB concentration decreases. Serum TFN concentrations are commonly measured directly. In rare situations when a direct measure is not available, TFN concentration can be estimated indirectly from measurement of total iron-binding capacity (in mcg/dL), where TFN (in mg/dL) = (total iron-binding capacity × 0.8) – 43. TFN is also an acute-phase reactant, and its concentration is increased in the presence of critical illness. Iron stores also affect serum TFN concentrations: in iron deficiency, hepatic TFN synthesis is increased, resulting in increased serum TFN concentrations irrespective of the patient’s nutrition status.

Prealbumin (transthyretin) is the transport protein for thyroxine and a carrier for retinol-binding protein. Prealbumin stores are low (10 mg/kg of body weight), and it has a very short half-life (2–3 days). The serum prealbumin concentration may be reduced after only a few days of a significant reduction in calorie and protein intake or in patients with severe metabolic stress (e.g., trauma, burns). It is most useful in monitoring the short-term, acute effects of nutrition support or deficits, as it responds very quickly in both situations. As with ALB and TFN, prealbumin synthesis is decreased in liver disease. Increased prealbumin concentrations may be seen in patients with kidney disease because of impaired excretion.

Immune Function Tests

Nutrition status affects immune function either directly, via actions on the lymphoid system, or indirectly by altering cellular metabolism or organs that are involved with immune system regulation. Immune function tests most often used in nutrition assessment are the total lymphocyte count and delayed cutaneous hypersensitivity (DCH) reactions. Both tests are simple, readily available, and inexpensive.

Total lymphocyte count reflects the number of circulating T and B lymphocytes. Tissues that generate T cells are very sensitive to malnutrition, undergoing involution resulting in decreased T-cell production and eventually lymphocytopenia. A total lymphocyte count less than 1,500 cells/mm3 (<1.5 × 109 cells/L) has been associated with nutrition depletion.2 DCH is commonly assessed using recall antigens to which the patient was likely previously sensitized, such as mumps and Candida albicans. Anergy is associated with severe malnutrition, and response is restored with nutrition repletion. Other immune function tests used in nutrition-related research include lymphocyte surface antigens (CD4, CD8, and the CD4:CD8 ratio), T-lymphocyte responsiveness, and various serum interleukin concentrations.

Total lymphocyte count is reduced in the presence of infection (e.g., human immunodeficiency virus [HIV], other viruses, tuberculosis), immunosuppressive drugs (e.g., corticosteroids, cyclosporine, tacrolimus, sirolimus, chemotherapy, antilymphocyte globulin), leukemia, and lymphoma. A number of factors affect DCH, including fever, viral illness, recent live virus vaccination, critical illness, irradiation, immunosuppressive drugs, diabetes mellitus, HIV, cancer, and surgery. Thus, a lack of specificity limits the usefulness of these tests as nutrition status markers. Nutrients such as arginine, omega-3 fatty acids, and nucleic acids given in pharmacologic doses may improve immune function. Monitoring efficacy of a nutrition care plan that includes these potentially immune-modulating nutrients may include immune function assessment with these or other immune function indicators.41,42

Specific Nutrient Deficiencies and Toxicities

Images A comprehensive nutrition assessment should include an evaluation for possible trace element, vitamin, and essential fatty acid deficiencies. Because of their key role in metabolic processes (as coenzymes and cofactors), a deficiency of any of these nutrients may result in altered metabolism and cell dysfunction. An accurate history to identify symptoms and risk factors for a specific nutrient deficiency is critical. A nutrition-focused physical examination for signs of deficiencies and biochemical assessment to confirm a suspected deficiency should be done in all at-risk patients. Ideally, biochemical assessment would be based on the nutrient’s function (e.g., metalloenzyme activity) rather than simply measuring the serum concentration. Unfortunately, few practical methods to assess micronutrient function are available; thus, the nutrient’s serum concentration is most often measured.

Trace Elements

Clinical syndromes are associated with a deficiency of the essential trace elements zinc, copper, manganese, selenium, chromium, iodine, fluoride, molybdenum, and iron in children and adults.4346 A deficiency state has not been recognized for tin, nickel, vanadium, cobalt, gallium, aluminum, arsenic, boron, bromine, cadmium, germanium, or silicon. Each trace element is involved in a variety of biologic functions and is necessary for normal metabolism, serving as a coenzyme or playing a role in hormonal metabolism or erythropoiesis. Toxicities can occur with excess intake of some trace elements. With the current public interest in complementary medicine, clinicians must ask patients about their use of dietary supplements and assess for signs and symptoms of toxicities as well as deficiencies (Table 118-6).

TABLE 118-6 Assessment of Trace Element Status


Zinc, the second most prevalent trace element, is a component of many enzymes and proteins and is involved in the regulation of gene expression, wound healing, and liver regeneration.47 Excess zinc intake is usually eliminated by the kidneys and GI tract; thus, zinc toxicity is uncommon except in overdose settings. Zinc deficiency is characterized by several signs and symptoms, including a moist eczematous dermatitis that is most apparent in the nasolabial folds and around orifices (Table 118-6). Recovery is rapid with oral zinc supplementation; severe dermatitis can remit in as little as 4 to 5 days.41 Zinc deficiency can be documented by the presence of low plasma zinc concentrations.48 However, plasma zinc concentrations decrease during acute stress states (trauma, surgery, burns, sepsis) and generally remain depressed until the stress resolves. Also, because zinc is a normal contaminant of most blood collection tubes, special zinc-free collection tubes must be used for plasma assays. Hair zinc analysis and urinary zinc excretion can also be used as biomarkers of zinc status.48

Copper is a component of ceruloplasmin and key metalloenzymes involved in iron metabolism (ceruloplasmin), electron transport and energy metabolism (cytochrome oxidase), connective tissue and collagen cross-linking (lysyl oxidase, elastase, and monamine oxidase), and free radical scavenging (superoxide dismutase). Copper intake in excess of metabolic requirements is excreted through the bile. Signs and symptoms of copper deficiency include hypochromic anemia, neutropenia, neurologic dysfunction, skeletal demineralization, and hypercholesterolemia (Table 118-6). In severe cases, such as in Menkes’ syndrome, copper deficiency is further manifested as hypothermia, hair and skin depigmentation, progressive mental deterioration, and growth retardation. Factors predisposing to copper deficiency include malabsorption states, protein-losing enteropathy, nephrotic syndrome, and copper-free parenteral nutrition.49 The chronic ingestion of too much copper or inadequate elimination can result in cirrhosis as seen in Wilson’s disease, an autosomal-recessive genetic disorder. Copper deficiency is best assessed using serum copper concentrations, which appear to reflect changes in copper status in both copper-depleted and copper-replete individuals.50 Serum copper concentrations may not accurately reflect total body copper status because serum concentrations may be altered by a variety of conditions (Table 118-6).

Trivalent chromium is an important cofactor, along with insulin, in the maintenance of normal blood glucose concentrations. Recent data indicate that a low-molecular-weight chromium binding substance, sometimes referred to as the glucose tolerance factor, may enhance the response of the insulin receptor to insulin.51 Chromium deficiency is characterized by glucose intolerance, impaired protein utilization, and increased insulin requirements. Patients with chromium deficiency also may have increased free fatty acid concentrations and a low respiratory quotient (RQ) (Table 118-6). Chromium deficiency has only been identified in patients receiving long-term parenteral nutrition with inadequate chromium intake. Plasma chromium concentrations do not accurately reflect total body chromium status, presumably because the biologically active form of chromium is the low-molecular-weight chromium binding substance. Toxicity from trivalent chromium is not a common clinical concern, and chromium toxicity has been reported only with contaminated drinking water or industrial exposure. Chromium supplementation as an adjunct for weight loss has not been proven effective.

Manganese is important in the function of many enzymes, including arginase (amino acid metabolism via the urea cycle), pyruvate carboxylase and phosphoenolpyruvate carboxykinase (carbohydrate and cholesterol metabolism), superoxide dismutase (mitochondrial antioxidant), glycosyltransferases (bone formation via proteoglycans), and prolidase (wound healing).43,46,52 Excess manganese is eliminated via the bile. Manganese deficiency has only been reported in association with the ingestion of chemically defined manganese-deficient oral diets. Table 118-6 lists common symptoms associated with manganese deficiency. Manganese toxicity is more concerning and has been described in industrial exposures via inhaled manganese and in patients receiving long-term parenteral nutrition supplemented with manganese (standard trace element preparation) in the setting of chronic cholestasis.43,46,5255Manganese can accumulate in brain tissue, and the newborn brain may be more susceptible to the effects of manganese toxicity.46,53 Whole-blood manganese concentrations can be obtained to assess manganese status. MRI with intensity and T1 values in the globus pallidus may be useful for assessing manganese toxicity.54,55Clinical toxicity is evidenced primarily by extrapyramidal symptoms mimicking Parkinson’s disease, such as tremors, ataxia, and facial muscle spasms. These symptoms may be preceded by psychiatric symptoms, including irritability, aggressiveness, and hallucinations. In most reported cases, manganese removal from the parenteral nutrition solution resulted in resolution of neurologic symptoms in 6 months with partial or total normalization of the MRI after 1 to 2 years.

Selenium is incorporated into at least 25 enzymes known as selenoproteins, about half of which have a defined metabolic function. Important selenoproteins include selenoprotein P (antioxidant activity), glutathione peroxidases (antioxidant activity), iodothyronine deiodinase (thyroid hormone regulation), thioredoxin reductase (vitamin C), selenoprotein V (spermatogenesis), and selenoprotein S (inflammation and immune response).4345,56 Selenoprotein P is the major (60%) circulating form of selenium in plasma. A key metabolic function of selenium has been attributed to its role in the enzymatic cofactor selenocysteine, the 21st amino acid.56 Prematurity, critical illness, chronic GI losses, and long-term selenium-free parenteral nutrition are associated with low serum selenium concentrations and decreased glutathione peroxidase activity.4345,56 The clinical significance of reduced serum selenium concentrations is unclear, but low selenium concentrations may make individuals more susceptible to physiologic stressors. Although higher selenium intakes are suggested for critically ill patients, the optimal intake is unknown. Current recommendations range from 20 to 1000 mcg/day.56 Low plasma selenium concentrations in critically ill patients correlate with low triiodothyronine (T3) concentrations.56 Serum selenium concentrations reflect acute distribution between tissues rather than selenium stores. Selenium deficiency is associated with muscle pain, wasting, and weakness (Table 118-6), but severe biochemical deficiency is not always accompanied by these symptoms. Fatal cardiomyopathy has been reported in several cases. Plasma, serum, erythrocyte, and whole-blood selenium, plasma selenoprotein P, and plasma, platelet, and whole-blood glutathione peroxidase activity respond to changes in selenium intake, but the response is heterogeneous.57 Decreased plasma selenium concentrations may indicate selenium deficiency, but reductions have been observed in patients with malignancies, liver failure, pregnancy, alcoholism, and HIV; in patients receiving statins or corticosteroids; and in smokers. Selenium toxicity or selenosis generally occurs only in those with long-term exposure to foods grown in selenium-rich soil (e.g., U.S. Great Plains area) and may occur when intake exceeds 400 mcg/day for prolonged periods; although, the lowest observed adverse event intake is 850 mcg/day. Selenium toxicity results in hair and nail brittleness and loss, GI disturbance, skin rash, garlic breath odor, fatigue, irritability, and nervous system abnormalities.

Molybdenum is a cofactor for enzymes involved in catabolism of sulfur amino acids, purines, and pyrimidines (i.e., xanthine, aldehyde, and sulfite oxidases).4345 Molybdenum deficiency is rare, but an inborn error of metabolism resulting in molybdenum deficiency has been identified. One case of molybdenum deficiency has been reported in a patient receiving long-term parenteral nutrition who presented with symptoms that included tachycardia, tachypnea, headache, night blindness, nausea, vomiting, central scotomas, lethargy, disorientation, and ultimately coma (Table 118-6). Symptoms were reversed when molybdenum was added to the parenteral nutrition solution.58 Factors predisposing to molybdenum deficiency appear to be low birth weight,59 excessive GI losses, and long-term inadequate intake, such as with molybdenum-free parenteral nutrition. Biochemical abnormalities expected in molybdenum deficiency include very low serum and urine uric acid concentrations (low xanthine oxidase activity) and low urine inorganic sulfate concentrations with high urine inorganic sulfite concentrations (low sulfate oxidase activity).4345 Molybdenum toxicity has not been described.

Deficiency of iodine, a component of thyroid hormones, may result in goiter formation (see Chap. 58). However, not everyone with an iodine-deficient diet will develop a goiter. Measurement of thyroxine (T4) and T3 can be used to assess iodine status (Table 118-6). IV iodine supplementation is not necessary except during long-term parenteral nutrition with minimal enteral intake. Iodine needs may be met by cutaneous absorption of iodine from germicides (e.g., povidone–iodine) used in catheter care or consumption of iodized salt.4345 Use of povidone–iodine as a topical antiseptic has decreased with the increased use of chlorhexidine for catheter care; thus, the need for iodine supplementation must be individualized. Iodine excess is rarely a clinical concern when thyroid and kidney function are normal.

Iron is the most abundant trace element and is an important component of hemoglobin, myoglobin, and cytochrome enzymes; it is important in oxygen transport and cellular energy production. Patients with iron-deficiency anemia generally present with fatigue, weakness, and pallor, but they may have other symptoms (see Chap. 80).4345 Inadequate iron intake, malabsorption, and blood loss are the principal causes of iron-deficiency anemia. Iron toxicity (overload) with possible organ damage can occur when chronic iron intake exceeds requirements, such as in patients receiving chronic blood transfusions. Iron deficiency or overload is confirmed by assessment of body iron stores, as reflected indirectly by measurement of hemoglobin, serum iron, total iron-binding capacity, and serum ferritin or directly by bone marrow staining or liver biopsy. Direct methods are the most accurate but are invasive and rarely necessary. Because indirect parameters may be altered by acute or chronic illness independent of iron stores, concomitant illness must be considered in their interpretation.


Vitamins act as both catalysts (cofactors) and substrates in essential metabolic reactions. A comprehensive nutrition-focused history and physical examination is the most valuable means of assessing patients for vitamin deficiency or toxicity (Table 118-7). A thorough review of vitamins and their complex effects on nutrition and metabolism is beyond the scope of this chapter.4345,60,61 Multiple vitamin deficiencies may be associated with generalized malnutrition; however, single vitamin deficiencies occur. Thiamine deficiency results in lactic acidosis and encephalopathy. Pernicious anemia caused by vitamin B12 (cyanocobalamin) deficiency can occur after ileal resection and has been reported with increasing frequency as a consequence of decreased gastric acidity, especially in elderly adults.62

TABLE 118-7 Assessment of Vitamin Status


The increasing prevalence of vitamin D deficiency is a growing U.S. healthcare concern, especially in children and elderly adults.6365 Laboratory assessment can confirm the clinical suspicion of a deficiency or toxicity state. The most common assessment is measurement of 25-OH-vitamin D, the storage form of vitamin D, in plasma or serum. Because 1,25-(OH)2-vitamin D is not stored and usually found in low concentrations in the blood because it is produced only when needed, it is not a useful marker of vitamin D deficiency (Table 118-7). The first indication of a deficiency is usually a decrease in circulating serum concentrations of 25-OH-vitamin D. Subsequently, there is a decrease in urinary excretion of vitamin D, which is followed by diminished tissue concentrations.

Vitamin toxicity can occur, especially with fat-soluble vitamins (A, D, E, and K), which are stored in the body. Excessive dietary vitamin A intake (hypervitaminosis A) is linked to an increased risk of hip fractures in both men and women.66,67 With the exception of cyanocobalamin, which is stored in the liver, water-soluble vitamins are not stored in the body; consequently, the risk of toxicity is minimal unless ingested in very high doses. Recent evidence, however, suggests that even water-soluble vitamins may be associated with adverse events when taken chronically in high doses. Although folic acid administration is definitively associated with a reduction in neural tube defects, its effect on some cardiac outcomes (as a result of its effect on homocysteine concentrations) is not established.68 The administration of folic acid, vitamin B6 (pyridoxine), and vitamin B12 after coronary artery stenting has been associated with an increased risk of stent restenosis.69 With Americans’ current use of nutrition supplements, clinicians should be alert for signs of hypervitaminosis (Table 118-7) and inappropriate vitamin use and discuss rational supplement use with all patients.

Essential Fatty Acids

The human body can synthesize all fatty acids except the essential fatty acids, linoleic acid (an omega-6 fatty acid) and α-linolenic acid (an omega-3 fatty acid). A deficiency state or essential fatty acid deficiency (EFAD) can be prevented if approximately 5% of total calories are ingested as these fatty acids.70,71 EFAD is rare in adults and children but can occur with prolonged use of lipid-free parenteral nutrition, severe fat malabsorption, very low-fat enteral feeding formulations or diets, high medium chain triglyceride-containing diets, and severe malnutrition, especially in stressed patients.71 Although the time course to develop EFAD is variable, overt EFAD has been shown to occur after 4 weeks of lipid-free parenteral nutrition, and biochemical evidence can occur within 1 week.71 Because newborns, especially those born prematurely, have limited fat stores, they may develop EFAD more rapidly than adults. Biochemical evidence of EFAD has been noted within 72 hours after birth in preterm infants receiving fat-free IV solutions.72 Symptoms reported with EFAD include dermatitis (dry, cracked, scaly skin), alopecia, impaired wound healing, growth failure, thrombocytopenia, and anemia.

Linoleic acid is converted to arachidonic acid (a tetraene fatty acid). When linoleic acid is unavailable, oleic acid is substituted, resulting in production of eicosatrienoic acid (a triene fatty acid) as the metabolic end product. Thus, EFAD can be detected by decreased tetraene production and increased triene production. The usual ratio of trienes to tetraenes is less than 0.4; when the ratio is greater than 0.4, the diagnosis of EFAD is established. Analysis of plasma fatty acids is expensive and not widely available; therefore, EFAD diagnosis is generally made based on risk assessment and clinical findings.


Carnitine is a quaternary amine required for transport of long-chain fatty acids into the mitochondria for β-oxidation and energy production. Carnitine also binds acyl residues aiding in their elimination (detoxification), thereby decreasing the number conjugated with coenzyme A and increasing the ratio of free to acetylated coenzyme A. Carnitine is available from a wide variety of dietary sources (especially meats) and can be synthesized by the liver and kidneys from lysine and methionine. Hepatic synthesis is decreased in premature infants, and low plasma carnitine concentrations and overt carnitine deficiency have been documented in premature infants receiving carnitine-free parenteral nutrition or diets, as well as in those with inborn errors of metabolism.73 Other predisposing factors for carnitine deficiency include chronic kidney74 or liver disease, chronic valproic acid and zidovudine use,75 and a vegetarian diet. The clinical presentation of carnitine deficiency includes generalized skeletal muscle weakness, fatty liver, and fasting hypoglycemia.73

In clinical practice, carnitine status is most often assessed by measurement of plasma total and free carnitine concentrations and acylcarnitine, although tissue concentrations, especially muscle, are higher than plasma concentrations.73 Plasma and urine carnitine concentrations are most helpful in primary carnitine deficiency (an inborn error of metabolism); acylcarnitine concentrations are more helpful in secondary causes of carnitine deficiency. When only total and free concentrations are available, the free is subtracted from the total to give the acylcarnitine concentration.


Images Nutrient requirements vary with age, gender, size, disease state, and clinical condition. Nutrition status, physical activity, and the need for continued maintenance of adequate nutrition or repletion in those with ongoing metabolic stress dictate the nutrient requirements for an individual. For obese patients, usual nutrition requirements may be altered because of the need for weight loss. In children, there is the added consideration of sustaining or reestablishing normal growth and development. Organ function (e.g., intestine, kidney, liver, pancreas) may affect nutrient utilization. Nutrient requirements can be estimated using guidelines interpreted in the context of patient-specific factors.

Recommended Dietary Allowances

The recommended daily allowances (RDAs) were initially established in 1941, but in 1997, the Food and Nutrition Board introduced a new family of nutrition reference values, the dietary reference intakes (DRIs).76 The four DRI categories are estimated average requirements (EARs), RDAs, adequate intakes (AIs), and tolerable upper intake levels (ULs). EARs, defined as the nutrient intake that meets the needs of 50% of persons in a given population, can be used for planning nutrient intakes for groups. The RDA, the nutrient intake that meets the needs of almost all persons in a designated group, is approximately 2 standard deviations above the EAR for nutrients for which the requirement is well defined and 1.2 times the EAR for other nutrients. To evaluate an individual’s daily intake, the RDA is the most appropriate comparator. AIs, defined as the average intake for the designated group that appears to sustain a particular nutrition state, growth, or other functional indicator of health, is reserved for nutrients for which no EAR or RDA has been determined. Finally, the UL is the maximum nutrient intake unlikely to pose adverse effects in almost all persons in a designated group.76

Dietary reference intakes have been established for six nutrient groups: calcium, phosphorus, magnesium, vitamin D, and fluoride; folate and other B vitamins; antioxidants (e.g., selenium and vitamins C and E); trace elements; macronutrients (e.g., protein, fat, carbohydrates, and fiber); and electrolytes and water.76 Because of the increased prevalence of vitamin D deficiency, calcium and vitamin D recommendations were revised in 2010.77 The U.S. Department of Agriculture’s website includes an Interactive DRI for Healthcare Professionals, which calculates a generally healthy individual’s DRI-based nutrition needs.78

According to the DRIs, adults should consume 45% to 65% of their total calories as carbohydrates (RDA, 130 g), 20% to 35% as fat, and 10% to 35% as protein.70 The recommendations for children are similar: carbohydrate, 45% to 65%; fat, 30% to 40%; and protein, 10% to 30%. Infants, especially premature infants, require a higher proportion of calories from fat (∼40%–50% of total calories) to ensure normal neurological development.


Images Energy requirements of individuals can be estimated using published, validated equations or can be measured directly. The most appropriate method is determined by a variety of factors, including severity of illness and resource availability.

Estimating Energy Expenditure

Daily energy expenditure consists of the basal energy expenditure (BEE), diet-induced thermogenesis (10%), and energy used for physical activity. In sick or injured patients, the BEE is increased because of stress-related hypermetabolism, but the physical activity and the energy needed for metabolism are usually reduced. For example, continuous infusion enteral feeding, often used in critically ill patients, results in minimal diet-induced thermogenesis (5%) when overfeeding is not present.19 Failure to account for these changes can result in overfeeding.

More than 200 methods for determining an individual’s daily energy requirement have been published. These methods use population estimates of calories per kilogram of body weight (kcal/kg), equations that estimate energy expenditure (kcal/day or kJ/day; 1 kcal is equivalent to 4.186 kJ), or indirect calorimetry. The simplest method to determine energy requirements is to use population estimates of calories required per kilogram of body weight. This method assumes standard values for health or the energy requirements associated with various disease states or clinical conditions, as well as the additional requirements for repletion of a malnourished individual. Most do not take into consideration age- or gender-related differences in energy needs. No stress or activity modifiers are used with these equations because the effect of the clinical condition (hypermetabolism) is already captured in the calculation. Daily adult requirements by this method can be estimated as shown below.2,19,7981

   1. Healthy, normal nutrition status, minimal illness severity: 20 to 25 kcal ABW/kg/day (84–105 kJ ABW/kg/day)

   2. Illness, metabolic stress (BMI <30 kg/m2): 25 to 30 kcal ABW/kg/day (105–126 kJ ABW/kg/day)

   3. Illness, metabolic stress (BMI ≥30 kg/m2): 11 to 14 kcal ABW/kg/day (46–59 kJ ABW/kg/day) or 22 to 25 kcal IBW/kg/day (92–105 kJ ABW/kg/day)

   4. Major burn injury (≥50% total body surface area) or repletion: 30 kcal ABW/kg/day or greater (≥126 kJ ABW/kg/day)

When equation 3 is used for patients with a BMI of 30 kg/m2 or more, the calories provided allow for permissive underfeeding (provision of approximately 80% of estimated or measured energy needs), which decreases infection rates and hospital length of stay.79 Table 118-8 shows suggested calorie intakes (kcal/kg) for maintenance and normal growth of healthy infants and children.70,71 These maintenance energy requirements are approximately 150% of the basal metabolic rate, with the additional calories provided to support usual activity and growth. For all ages, energy requirements increase with fever, sepsis, major surgery, trauma, burns, and long-term growth failure and in the presence of chronic conditions such as bronchopulmonary dysplasia, congenital heart disease, and cystic fibrosis. Energy needs may decrease with obesity and neurologic disability (e.g., cerebral palsy).22

TABLE 118-8 Dietary Reference Intakes for Energy and Protein in Healthy Children


Numerous equations are available to estimate energy expenditure in adults and children (Tables 118-9 and 118-10, respectively).2,19,70,71,79,81,82 The Harris-Benedict equations, derived in 1919 in a study of 239 individuals, are still used for assessing energy requirements in adults. They have the advantage of incorporating the patient’s age, height, weight, gender, and clinical condition into the estimation. These equations were derived from oxygen consumption measurements made on normally nourished healthy individuals who were in a fasting and resting state. Although these equations are commonly referred to as the “BEE equations,” they actually estimate resting energy expenditure (REE), the amount of energy expended at rest by a fasting, awake individual in a temperature-controlled environment performing only basal functions such as breathing, circulation, and metabolic processes.

TABLE 118-9 Estimates of Energy Expenditure in Adults a


TABLE 118-10 Equations to Estimate Energy Expenditure in Children a,b


Because these equations approximate REE, their results must be modified by a factor that adjusts for the individual’s clinical condition. For example, whereas an individual who is confined to bed may require a calorie intake that is only 20% to 30% above the REE, a person who has sustained a severe burn injury may require 150% to 200% of the calculated REE. Some clinicians multiply the calculated REE by both a stress factor and an activity factor. Because validation studies in healthy subjects have shown that these equations overestimate REE by 6% to 15%, the calculated REE should be multiplied by either a stress factor or an activity factor to avoid further overestimation of the individual’s energy needs.2 It should also be noted that ABW (up to a BMI of 57 kg/m2 in men and 40 kg/m2 in women), not IBW or adjusted body weight, was used to generate the original data with these equations and should be used for these calculations.81 Overestimation of energy needs with the Harris-Benedict equations is well documented.19,81 The Mifflin-St Jeor equations are more accurate in healthy adults than the Harris-Benedict equations (Table 118-9): the accuracy rate is 80% in patients who are not obese (BMI ≤30 kg/m2) and 70% in obese patients (BMI >30 kg/m2).19

There is no individual method proven to accurately determine the energy needs of all critically ill patients. The Penn State equations are more accurate in critically ill adults receiving mechanical ventilation19(Table 118-9). There is no consensus as to the best equation for critically ill adults who are not mechanically ventilated. Likewise, there is insufficient evidence to support the use of one equation over another in estimating the energy expenditure of critically ill children.83,84 The metabolic response to stress in children appears to be similar to that seen in critically ill adults; thus, “stress factors” used in adults, shown in Table 118-11, are often used in children after the energy expenditure has been estimated using one of the predictive equations shown in Table 118-10.

TABLE 118-11 Stress Factors for Use in Adults and Children


Clinical Controversy…

Numerous equations and “stress” factors have been published for estimating energy requirements. None is superior in all situations. Practitioners vary as to which equation they choose to use for any given patient.

Measuring Energy Expenditure

The most accurate method to determine energy expenditure is to measure it using indirect calorimetry (metabolic gas monitoring); however, because of lack of access to necessary equipment, it is used in only a small fraction of patients receiving nutrition support. The indirect calorimetry methodology is based on pulmonary gas exchange: when a substrate (carbohydrate, fat, protein) is oxidized, heat is produced, oxygen is consumed, and carbon dioxide is expired in specific amounts depending on the substrate being oxidized. Indirect calorimetry is a noninvasive procedure in which oxygen consumption (VO2, mL/min) and carbon dioxide production (VCO2, mL/min) are measured, and the measured resting energy expenditure (MREE; kcal/day) is calculated using the abbreviated Weir equation as MREE = ([3.94 VO2 + 1.11 VCO2] + [2.17 uN2]) × 1.44.85,86 The urinary nitrogen component (uN2) is often omitted when calculating energy expenditure because it accounts for less than 4% of the energy expenditure in critically ill patients, and its omission results in only a 1% to 2% calculation error.19,86 Excluding the nitrogen component obviates the need for a 24-hour urine collection, which can be problematic in many patients.

The MREE represents the total energy expended during the time period over which the measurements were taken. It is often extrapolated to a 24-hour period to approximate daily energy requirements. MREE reflects alterations in energy requirements as a result of disease or clinical condition, but it does not include energy required for repletion of a malnourished individual or growth in a child. The energy intake required for these functions is accounted for by multiplying MREE by a metabolic or activity factor: mechanically ventilated, critically ill, 1; critically ill, no mechanical ventilation, 1 to 1.1; adult acute, not critically ill, 1.1 to 1.4, depending on activity; adult needing repletion or a child, 1.3 to 2; adult outpatient, 1.1 to 2, depending on activity; and adult depletion (weight loss), less than 1.87

Indirect calorimetry can be used to determine the patient’s RQ, which reflects substrate oxidation, characterizes substrate utilization, and is calculated as VCO2/VO2. RQ values for nutrient substrates are fat, 0.7; carbohydrate, 1; protein, 0.8; and mixed substrate (fat, carbohydrate, and protein), 0.85. RQ values of greater than 1 represent either lipogenesis or hyperventilation; less than 0.7 may indicate a ketogenic diet, fat gluconeogenesis, or ethanol oxidation. Values outside the physiologic range of 0.67 to 1.3 suggest an invalid test. Clinically, the RQ is used to determine if a patient is being overfed, which is likely if the RQ value is greater than 1.

Indirect calorimetry is a respiratory measurement that does not reflect metabolism in all clinical situations.81,8587 Calibration errors are common, and indirect calorimetry overestimates REE for patients with hyperventilation, metabolic acidosis, overfeeding, and if there are air leaks anywhere in the system. Underestimation of REE is likely with hypoventilation, metabolic alkalosis, underfeeding, and gluconeogenesis. Mechanically ventilated patients are technically easier to study because the indirect calorimeter circuit can be integrated into the ventilator circuit. However, the patient must be at complete rest for 1 hour, must not receive bolus feedings either by feeding tube or orally for 4 hours, should have no changes in substrate delivery for 12 hours, and must be on a fraction of inspired O2 of less than 0.6 with a positive end-expiratory pressure less than 5 cm H2O to ensure a steady-state reading. Unfortunately, many of the patients in whom indirect calorimetry would be most useful will not meet these requirements. Indirect calorimetry should be considered in any patient in whom uncertainty in estimating energy requirements needs to be minimized, such as severely malnourished patients (BMI <18.5 kg/m2) or obese patients (BMI >30 kg/m2), patients with unexplained high partial arterial pressure of carbon dioxide (PaCO2) concentrations or minute ventilation, patients with spinal cord injuries, and patients who experience weight loss despite apparently receiving adequate protein and energy intakes.19,79,85 In the outpatient setting, the availability of portable, less expensive devices has allowed an increase in indirect calorimetry use in weight management.88


Daily protein requirements are based on age, gender, nutrition status, disease state, and clinical condition. Table 118-8 lists the RDAs for protein for children; for individuals older than 18 years of age, the RDA is 0.8 g/kg/day, which is significantly less than most Americans typically consume.70 In adults older than 60 years of age, protein needs are increased to 1 to 1.5 g/kg/day to help reduce loss of LBM that occurs with aging, and 1.5 to 2 g/kg/day or more may be needed in states of metabolic stress (infection, trauma, surgery) to prevent loss of LBM.70,79,89 Protein requirements are also higher in pregnant and lactating women (1.1 g/kg/day or 6–10 g protein per day above the usual RDA).70,90

Protein metabolism depends on both kidney and liver function. Critical illness results in a hypercatabolic state in which there is increased protein synthesis and degradation. The goal of protein administration is to minimize catabolism by maximizing protein synthesis. Consequently, protein requirements are increased to 1.2 to 2 g/kg/day in critically ill patients. For obese critically ill patients, protein needs are 2 g/kg IBW or more if the BMI is between 30 and 40 kg/m2 and 2.5 g/kg IBW or more if the BMI is greater than 40 kg/m2.79 Adults with significant total body surface area burns have protein requirements as high as 2.5 to 3 g/kg ABW/day. In children with significant burns, between 20% and 25% of their total calorie needs should be provided as protein.80 Soft tissue defects and large stool or ileostomy losses also increase protein requirements. Liver failure typically results in the need for protein restriction (0.5 g/kg/day) unless a hypercatabolic state is also present, which will increase requirements to 1.5 g/kg/day. Protein needs in patients with kidney failure are variable and affected by the various renal replacement therapies available. The application of these protein intake guidelines requires both clinical judgment and frequent monitoring of kidney and liver function, serum chemistries, clinical condition, and nutrition outcomes.

Nitrogen is found only in protein and at a relatively constant ratio of 1 g nitrogen per 6.25 g of protein. This ratio may vary somewhat for enteral and parenteral feeding formulations, depending on the biologic value of the protein source. The adequacy of protein intake can be assessed clinically by a nitrogen balance study—measuring urinary nitrogen excretion and comparing it with nitrogen intake. Nitrogen balance indirectly reflects protein use or protein catabolic rate, which increases with hypercatabolism. As the stress level increases, a concomitant increase in protein catabolism results in an increase in urinary nitrogen excretion. Usually the amount of urine urea nitrogen (UUN) is measured in a 24-hour urine collection. In healthy individuals, UUN accounts for 80% to 90% of the total urine nitrogen (TUN) excreted. Nitrogen output (g/day) can be approximated as 24-hour UUN + 4, where 4 is a factor representing usual skin, fecal, and respiratory nitrogen losses. Alternatively, if available, TUN can be measured and may be more accurate, especially in critically ill patients. If TUN is used, then the best estimate of nitrogen output is TUN × 1.05.91 In patients with kidney failure, in which case neither UUN nor TUN accurately represents net protein degradation, nitrogen balance can be approximated with equations based on urea nitrogen appearance.92


The daily AI for men and women for α-linolenic acid is 1.6 and 1.1 g, respectively; for linoleic acid, it is 14 to 17 g/day for men and 11 to 12 g/day for women.70 Overall, for adults, fat should represent no more than 10% to 35% of total calories, with the recommendation that saturated fatty acids, trans fatty acids, and dietary cholesterol intake be kept as low as possible while a nutritionally adequate diet is consumed. Fat should constitute 30% to 40% of energy in children 1 to 3 years of age and 25% to 35% of energy in children 4 to 18 years of age.70 Fat intake in children younger than 3 years of age is critical for proper central nervous system growth and development; generally, fat-restricted diets (e.g., skim milk) should not be imposed until after the age of 2 to 3 years except under medical supervision. A lower limit of 15% of total energy intake has been suggested as the minimum fat intake in children when fat restriction is warranted.93


Lower blood pressure and serum cholesterol concentrations as well as maintenance of normal bowel habits have been attributed to dietary fiber intake. Fiber intake may also have a role in the prevention of colon cancer and may promote weight control through its effect on satiety. Men and women 50 years of age and younger should ingest 38 g/day and 25 to 26 g/day, respectively, of total fiber. For men and women older than 50 years of age, the recommended intakes are 30 g/day and 21 g/day, respectively.70,94 The AI for fiber has not been set for children younger than 1 year of age. For older children, the recommended fiber intake is 19 g/day for children 1 to 3 years of age, 24 g/day for children 4 to 8 years of age, and 26 to 31 g/day for children 9 to 13 years of age.70 Another method to determine fiber need in children is the “age + 5” rule. The recommended daily intake of fiber is calculated by adding 5 g to the child’s age in years.95 Using this rule, a 6-year-old child would need 11 g/day of dietary fiber.


The daily fluid requirement for an adult depends on many factors but is generally estimated to be 30 to 35 mL/kg, 1 mL for each kcal ingested, or 1,500 mL/m2. Fluid requirements per kilogram of body weight are higher for children and even higher for preterm infants because of their higher percentage of TBW and basal energy needs. Additionally, premature neonates have increased fluid requirements because of greater insensible losses and the kidneys’ inefficiency in concentrating urine. The Holliday-Segar method is a commonly used, quick, and simple method for estimating minimum daily fluid needs of children and adults. Children weighing less than 10 kg should receive at least 100 mL/kg per day. An additional 50 mL/kg/day should be provided for each kilogram of body weight between 11 kg and 20 kg and 20 mL/kg/day for each kilogram above 20 kg. Thus, whereas minimum daily fluid needs for a child weighing 8 kg would be 800 mL/day; 1,350 mL/day would be needed for a 17-kg child, and 2000 mL/day is needed for a 50-kg individual.

Table 118-12 lists factors that alter fluid needs for both adults and children. All sources of fluid intake should be assessed (e.g., fluid vehicles for IV medications and IV or feeding tube flushes) when determining fluid requirements. Urine output and specific gravity as well as serum electrolytes and weight changes can be used to assess fluid status. A urine output of at least 1 mL/kg/hr (in children) and approximately 40 to 50 mL/hr (in adults) is considered adequate to ensure tissue perfusion. Urine output should be higher if large fluid volumes or high renal solute loads (e.g., parenteral nutrition or concentrated enteral feeding formulations) are being administered. Urine specific gravity depends on the kidney’s concentrating and diluting capabilities. Concomitant diuretic therapy, as a result of increased solute excretion, limits the usefulness of urine specific gravity as an index of fluid status.

TABLE 118-12 Factors That Alter Fluid Requirements



Requirements for micronutrients (i.e., electrolytes, minerals, trace elements, and vitamins) vary with age, gender, and the route by which the nutrient is ingested (Table 118-13; see Chaps. 34 to 36).4346,60,61,77,96 Oral and parenteral requirements vary as a result of bioavailability considerations. Micronutrients poorly absorbed via the GI tract usually are required in greater amounts enterally than parenterally. However, many water-soluble micronutrients are excreted more rapidly via the kidneys when administered IV. In these situations, the IV dose is greater than the oral dose. Other factors that affect micronutrient requirements include GI losses through diarrhea, vomiting, or high-output fistula; wound healing; and hypermetabolism or hypercatabolism. Cutaneous micronutrient losses (e.g., zinc, copper, selenium) also may be significant after major burn injury. Sodium, potassium, magnesium, and phosphorus excretion are particularly dependent on kidney function, and in the setting of kidney failure, intake will likely need to be restricted. Calcium needs, on the other hand, may be increased in these patients. (See Chaps. 28 and 29.) Patients who are severely malnourished will have increased electrolyte requirements during early refeeding owing to preexisting deficiencies or rapid intracellular uptake with anabolism. Failure to provide adequate electrolyte replacement, especially phosphorus, and vitamin supplementation before delivery of full calories during refeeding has resulted in death from the refeeding syndrome.97,98

TABLE 118-13 Recommended Daily Electrolytes, Trace Elements, and Vitamins Intakesa



Drug–Nutrient Interactions

Images Drug-induced nutrient deficiency, poor therapeutic response, enhanced drug toxicity, and failure to achieve desired nutrition outcomes can occur if either nutrition support or drug therapy is stopped as a consequence of adverse effects. Patient outcomes may be enhanced when an effective screening method to identify significant drug–nutrient interactions is coupled with a patient counseling program. An important part of the screening process is to recognize risk factors that influence drug–nutrient interactions. The potential for drug–nutrient interactions is greatest in pediatric and elderly individuals, those with poor nutrition status (obesity and marasmus), and those receiving multiple drug therapies or tube feedings.99103

Mineral and electrolyte serum concentrations may change because of drug therapy. For example, with loop diuretics, urine sodium, potassium, calcium, and magnesium wasting may occur, causing a reduction in their respective serum concentrations (see Chaps. 34 to 36). Alternatively, calcium excretion is reduced with thiazide diuretics. Serum electrolyte concentrations also may increase as a direct result of the drug’s mechanism (e.g., potassium-sparing diuretics) or because of the drug’s salt form. Corticosteroids and cyclosporine are known to cause hyperglycemia; other drugs are prescribed to pharmacologically lower blood glucose concentrations (e.g., insulin and oral hypoglycemics) (see Chap. 57).

Vitamin status also may be affected by drugs (Table 118-14). For example, sulfasalazine therapy causes a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamine concentrations. Drug therapy outcomes also may be affected by vitamin intake. Whereas the ingestion of high folic acid doses may decrease methotrexate’s therapeutic effect, changes in an individual’s usual vitamin K or vitamin E intake may cause variability in warfarin’s anticoagulant effects.

TABLE 118-14 Drug and Vitamin Interactions


Drug-delivery vehicles also may contain nutrients. Most IV therapies (maintenance IV fluids, drugs, and electrolyte replacements) are delivered using either dextrose (e.g., dextrose 5% or 10% in water) or sodium (e.g., 0.9% normal saline) in the admixture. Lipid emulsion (10%) is used as the vehicle for the anesthetic agent propofol and the IV calcium channel blocker clevidipine and contributes fat calories (1.1 kcal/mL or 4.6 kJ/mL) when continuous infusions are used. In these instances, nutrition support regimens must be adjusted to accommodate these calories and other nutrients delivered through these therapies to avoid overfeeding and other complications.

Practical Guidelines for Nutrition Assessment

The value of any marker used for nutrition assessment is only as good as its ability to accurately identify the patient with malnutrition and to correlate with nutrition-related complications. The response of the various nutrition status markers to nutrition therapy and the correlation between improvement in these markers and decreased morbidity and mortality support their validity. However, when applied to an individual, most of these markers lack specificity and sensitivity, which makes the development of a clinically useful, cost-effective approach to an individual patient nutrition assessment challenging.

The importance of the nutrition-focused history and physical examination in both nutrition screening and nutrition assessment cannot be overemphasized. The minimum amount of objective data that can further substantiate the clinical impression and provide a baseline for subsequent monitoring is markers that show the best correlation with outcome: weight and serum ALB concentration. The cost effectiveness of the addition of other biochemical parameters is unknown. The assessment of other anthropometric measures is most useful in the setting of anticipated long-term nutrition support in which these measurements will serve as a longitudinal marker of response to the nutrition care plan.

Initially, nutrition requirements are determined on the basis of assumptions made about the patient’s clinical condition and the nutrition needs associated with repletion or growth, if needed. After a nutrition intervention has been initiated, periodic reassessment of nutrition status is critical to determine the accuracy of the initial estimate of nutrition requirements. Nutrition requirements are dynamic in the setting of acute or critical illness—as the patient’s clinical status changes, so will protein and energy requirements, further emphasizing the need for continued reassessment.

Better markers of nutrition status and methods for determining patient-specific nutrition requirements are needed to allow further refinement of estimates of an individual’s nutrition needs. Functional tests and simple, noninvasive tests for body composition analysis hold promise for the future. However, until better methods of assessment become available clinically and are demonstrated to be cost effective, the currently available battery of tests will continue to be the mainstay of nutrition assessment.





    1. Jensen GL, Hsiao PY, Wheeler D. Adult nutrition assessment tutorial. J Parenter Enteral Nutr 2012;36:267–274.

    2. DeLegge MH, Drake LM. Nutritional assessment. Gastroenterol Clin North Am 2007;36:1–22.

    3. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA 2012;307:491–497.

    4. Centers for Disease Control and Prevention. Overweight and Obesity: Adult Obesity Facts. 2013,

    5. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA 2012;307:483–490.

    6. Centers for Disease Control and Prevention. Growth Charts. 2010,

    7. Food and Drug Administration and National Institutes of Health. Final review. Healthy People 2010: Nutrition and Overweight. 2013,

    8. Charney P. Nutrition screening vs nutrition assessment: How do they differ? Nutr Clin Pract 2008;23:366–372.

    9. Soeters PB, Reijven PLM, van Bokhorst-de van der Schueren MAE, et al. A rational approach to nutritional assessment. Clin Nutr 2008;27:706–716.

   10. Joint Commission on Accreditation of Healthcare Organizations. Comprehensive Accreditation Manual for Hospitals: 2012 (Edition). Oakbrook Terrace, IL: Joint Commission Resources. 2012,

   11. Kondrup J, Allison SP, Elia M, et al. ESPEN guidelines for nutrition screening 2002. Clin Nutr 2003;22:415–421.

   12. Jensen GL, Hsiao PY, Wheeler D. Nutrition screening and assessment. In: Mueller C, ed. The A.S.P.E.N. Adult Nutrition Support Core Curriculum, 2nd ed. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 2012:155–169.

   13. Skipper A, Ferguson M, Thompson K, et al. Nutrition screening tools: An analysis of the evidence. J Parenteral Enteral Nutr 2012;36:292–298.

   14. Anthony PS. Nutrition screening tools for hospitalized patients. Nutr Clin Pract 2008;23:373–382.

   15. Centers for Disease Control and Prevention. Use of World Health Organization and CDC growth charts for children aged 0-59 months in the United States. Morbid Mortal Week Report 2010;59(RR-9):1–16.

   16. Makhija S, Baker J. The subjective global assessment: A review of its use in clinical practice. Nutr Clin Pract 2008;23:405–409.

   17. Keith J. Bedside nutrition assessment past, present, and future: A review of the subjective global assessment. Nutr Clin Pract 2008;23:410–416.

   18. Bauer JM, Kaiser MJ, Anthony P, et al. The Mini Nutritional Assessment®: Its history, today’s practice, and future perspectives. Nutr Clin Pract 2008;23:388–396.

   19. Frankenfield DC, Ashcraft CM. Estimating energy needs in nutrition support patients. J Parenter Enteral Nutr 2011;35:563–570.

   20. Hickson M, Frost G. A comparison of three methods for estimating height in the acutely ill elderly population. J Hum Nutr Diet 2003;16:13–20.

   21. Bell KL, Davies PS. Prediction of height from knee height in children with cerebral palsy and non-disabled children. Ann Hum Biol 2006;33:493–499.

   22. Marchand V, Motil KJ, and the NASPGHAN Committee on Nutrition. Nutrition support for neurologically impaired children: A clinical report of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2006;43:123–135.

   23. Chumlea WC, Guo SS, Steinbaugh ML. Prediction of stature from knee height for black and white adults and children with application to mobility-impaired or handicapped persons. J Am Diet Assoc 1994;94:1385–1388.

   24. Fenton TR. A new growth chart for preterm babies: Babson and Benda’s chart updated with recent data and a new format. BMC Pediatrics 2003;3:13.

   25. Rao SC, Tompkins J, World Health Organization. Growth curves for preterm infants. Early Human Dev 2007;83:643–651.

   26. Cronk C, Crocker AC, Pueschel SM, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics 1988;81:102–110.

   27. Centers for Disease Control and Prevention. Body Mass Index. 2011,

   28. Cook Z, Kirk S, Lawrenson S, Sandford S. Use of BMI in the assessment of undernutrition in older subjects: Reflecting on practice. Proc Nutr Soc 2005;64:313–317.

   29. Ness-Abramof R, Apovian CM. Waist circumference measurement in clinical practice. Nutr Clin Pract 2008;23:397–404.

   30. Klein S, Allison DB, Heymsfield SB, et al. Waist circumference and cardiometabolic risk: A consensus statement from Shaping American’s Health: Association for Weight Management and Obesity Prevention; NAASO, The Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care 2007;30:1647–1652.

   31. Fernández JR, Redden DT, Pietrobelli A, Allison DB. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 2004;145:439–444.

   32. Maffeis C, Banzato C, Talamini G, on behalf of the Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology. Waist-to-height ratio, a useful index to identify high metabolic risk in overweight children. J Pediatr 2008;152:207–213.

   33. Buchholz AC, Bartok C, Schoeller DA. The validity of bioelectrical impedance models in clinical populations. Nutr Clin Pract 2004;19:433–446.

   34. Willett K, Jiang R, Lenart E, et al. Comparison of bioelectrical impedance and BMI in predicting obesity-related medical conditions. Obesity (Silver Spring) 2006;14:480–490.

   35. Schlüssel MM, dos Anjos LA, de Vasconcellos MTL, et al. Reference values of handgrip dynamometry of healthy adults: A population-based study. Clin Nutr 2008;27:601–607.

   36. Budziareck MB, Duerte RRP, Barbosa-Silva MCG. Reference values and determinants for handgrip strength in healthy subjects. Clin Nutr 2008;27:357–362.

   37. Kerr A, Syddall HE, Cooper C, et al. Does admission grip strength predict length of stay in hospitalized older patients? Age Ageing 2006;35:82–84.

   38. Lee SY, Gallagher D. Assessment methods in human body composition. Curr Opin Clin Nutr Metab Care 2008;11:566–572.

   39. Baracos V, Caserotti P, Earthman CP, et al. Advances in the science and application of body composition measurement. J Parenter Enteral Nutr 2012;36:96–107.

   40. Crook MA. Hypoalbuminemia: The importance of correct interpretation. Nutrition 2009;25:1004–1005.

   41. Grimble RF. Immunonutrition. Curr Opin Gastroenterol 2006;21:216–222.

   42. Kudsk KA. Immunonutrition in surgery and critical care. Annu Rev Nutr 2006;26:463–479.

   43. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary Reference Intakes: Elements. 2009,

   44. Clark SF. Vitamins and trace elements. In: Mueller C, ed. The A.S.P.E.N. Adult Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 2012:121–154.

   45. Sriram K, Lonchyna VA. Micronutrient supplementation in adult nutrition therapy: Practical considerations. J Parenter Enteral Nutr 2009;33:548–562.

   46. Kleinman RE, ed. Trace elements. In: Pediatric Nutrition Handbook, 6th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2009:423–451.

   47. Mohommad MA, Zhou Z, Cave M, et al. Zinc and liver disease. Nutr Clin Prac 2012;27:8–20.

   48. Lowe NM, Fekete K, Decsi T. Methods of assessment of zinc status in humans: A systematic review. Am J Clin Nutr 2009;89(Suppl):2040S–2051S.

   49. Hurwitz M, Garcia MG, Poole RL, Kerner JA. Copper deficiency during parenteral nutrition: A report of four pediatric cases. Nutr Clin Pract 2004;19:305–308.

   50. Harvey LJ, Ashton K, Hooper L, et al. Methods of assessment of copper status in humans: A systematic review. Am J Clin Nutr 2009;89(Suppl):2009S–2024S.

   51. Vincent JB. Quest for the molecular mechanism of chromium action and its relationship to diabetes. Nutr Rev 2000;58:67–72.

   52. Dickerson RN. Manganese intoxication and parenteral nutrition. Nutrition 2001;17:689–693.

   53. Erikson KM, Thompson K, Aschner J, Aschner M. Manganese neurotoxicity: A focus on the neonate. Pharmacol Ther 2007;113:369–377.

   54. Iinuma Y, Kubota M, Uchiyama M, et al. Whole-blood manganese levels and brain manganese accumulation in children receiving long-term home parenteral nutrition. Pediatr Surg Int 2003;19:268–272.

   55. Takagi Y, Okada A, Sando K, et al. Evaluation of indexes of in vivo manganese status and the optimal intravenous dose for adult patients undergoing home parenteral nutrition. Am J Clin Nutr 2002;75:112–118.

   56. Hardy G, Hardy I, Manzanares W. Selenium supplementation in the critically ill. Nutr Clin Prac 2012;27:21–33.

   57. Ashton K, Hooper L, Harvey LJ, et al. Methods of assessment of selenium status in humans: A systematic review. Am J Clin Nutr 2009;89(Suppl):2025S–2039S.

   58. Sardesai VM. Molybdenum: An essential trace element. Nutr Clin Pract 1993;8:277–281.

   59. Friel JK, MacDonald AC, Mercer CN, et al. Molybdenum requirements in low-birth-weight infants receiving parenteral and enteral nutrition. J Parenter Enteral Nutr 1999;23:155–159.

   60. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary Reference Intakes: Vitamins. 2009,

   61. Kleinman RE, ed. Vitamins. In: Pediatric Nutrition Handbook, 6th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2009:453–495.

   62. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr 2009;89(Suppl):693S–696S.

   63. Wagner CL, Greer FR. American Academy of Pediatrics Section on Breastfeeding and Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008;122:1142–1152.

   64. Reis JR, von Mühlen D, Miller ER, et al. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics 2009;124:e371–e379.

   65. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–281.

   66. Peskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287:47–54.

   67. Michaëlsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003;348:287–294.

   68. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567–1577.

   69. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673–2681.

   70. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. 2005,

   71. Hise M, Brown JC. Lipids. In: Mueller C, ed. The A.S.P.E.N. Adult Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 2012:63–82.

   72. Foote KD, MacKinnon MJ, Innis SM. Effect of early introduction of formula versus fat-free parenteral nutrition on essential fatty acid status of preterm infants. Am J Clin Nutr 1991;54:93–97.

   73. Crill CM, Helms RA. The use of carnitine in pediatric nutrition. Nutr Clin Prac 2007;22:204–213.

   74. Schreiber B. Levocarnitine and dialysis: A review. Nutr Clin Prac 2005;20:218–243.

   75. Scruggs ER, Dirks Naylor AJ. Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy. Pharmacology 2008;82:83–88.

   76. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary Reference Intakes (DRIs): The Development of DRIS 1994-2004: Lessons Learned and New Challenges. 2008,

   77. Food and Nutrition Board. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Report brief. November 2010,

   78. United States Department of Agriculture, National Agriculture Library. Interactive DRI for Healthcare Professionals. 2013,

   79. McClave SA, Martindale RG, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). J Parenter Enter Nutr 2009;33:277–316.

   80. Chan MM, Chan GM. Nutrition therapy for burns in children and adults. Nutrition 2009;25:261–269.

   81. Wooley JA, Frankenfield D. Energy. In: Mueller C, ed. The A.S.P.E.N. Adult Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 2012:22–35.

   82. FAO/WHO/UNU Expert Consultation. Food and Nutrition Technical Report Series. Human Energy Requirements. October 2001;1–103,

   83. Meyer R, Kulinskaya E, Briassoulis G, et al. The challenge of developing a new predictive formula to estimate energy requirements in ventilated critically ill children. Nutr Clin Pract 2012;27:669–676.

   84. Mehta NM, Compher C, A.S.P.E.N. Board of Directors. A.S.P.E.N. clinical guidelines: Nutrition support of the critically ill child. J Parenter Enteral Nutr 2009;33:260–276.

   85. Haugen HA, Chan L-N, Li F. Indirect calorimetry: A practical guide for clinicians. Nutr Clin Pract 2007;22:377–388.

   86. Moreira de Rocha EE, Alves VGF, da Fonseca RBV. Indirect calorimetry: Methodology, instruments and clinical application. Curr Opin Clin Nutr Metab Care 2006;9:247–256.

   87. Holdy KE. Monitoring energy metabolism with indirect calorimetry: Instruments, interpretation, and clinical application. Nutr Clin Pract 2004;19:447–454.

   88. Rubenbauer JR, Johannsen DL, Baier SM, et al. The use of a handheld calorimetry unit to estimate energy expenditure during different physiological conditions. J Parenter Enteral Nutr 2006;30:246–250.

   89. Wolfe RR, Miller SL, Miller KB. Optimal protein intake in the elderly. Clin Nutr 2008;27:675–684.

   90. Duggleby SL, Jackson AA. Protein, amino acid and nitrogen metabolism during pregnancy: How might the mother meet the needs of her fetus? Curr Opin Clin Nutr Metab Care 2002;5:503–509.

   91. Velasco N, Long CL, Otto DA, et al. Comparison of three methods for the estimation of total nitrogen losses in hospitalized patients. J Parenter Enteral Nutr 1990;14:517–522.

   92. Wolk R, Foulks C. Renal disease. In: Mueller C, ed. The A.S.P.E.N. Adult Nutrition Support Core Curriculum. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 2012:491–510.

   93. Kleinman RE, ed. Fats and fatty acids. In: Pediatric Nutrition Handbook, 6th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2009:357–386.

   94. American Dietetic Association. Position of the American Dietetic Association: Health implications of dietary fiber. J Am Diet Assoc 2002;102:993–1000.

   95. Dwyer JT. Dietary fiber for children: How much? Pediatrics 1995;96:1019–1022.

   96. Greene HL, Hambidge KM, Schanler R, Tsang RC. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants and children receiving total parenteral nutrition: Report of the Subcommittee on Pediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr 1988;48:1324–1342.

   97. Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding syndrome. Nutr Clin Pract 2005;20:625–633.

   98. Skipper A. Refeeding syndrome or refeeding hypophosphatemia: A systematic review of cases. Nutr Clin Prac 2012;27:34–40.

   99. Jefferson JW. Drug and diet interactions: Avoiding therapeutic paralysis. J Clin Psychiatry 1998;59:31–39.

  100. Saito M, Hirata-Koizumi M, Matsumoto M, et al. Undesirable effects of citrus juice on the pharmacokinetics of drugs: focus on recent studies. Drug Saf 2005;28:677–694.

  101. Santos CA, Boullata JI. An approach to evaluating drug-nutrient interactions. Pharmacotherapy 2005;25:1789–1800.

  102. McCabe BJ. Prevention of food–drug interactions with special emphasis on older adults. Curr Opin Clin Nutr Metab Care 2004;7:21–26.

  103. Hester EK. HIV medications: An update and review of metabolic complications. Nutr Clin Prac 2012;27:51–64.