Current Geriatric Diagnosis & Treatment, 1st Edition

Section IV - Special Situations

38. Nutrition & Failure to Thrive

Larry E. Johnson MD, PhD

Dennis H. Sullivan MD

CHANGES IN BODY COMPOSITION & ENERGY REQUIREMENTS WITH AGING

The human body is made of lean mass (skeletal muscle, viscera, cells of blood and immune system; 35–50% of body weight); fat (20–30%); extracellular fluid (20%); and bone and connective tissue (10–15%). Body weight in men tends to increase from age 30–60, plateaus for 10–15 years, and then slowly declines. In women, the pattern of weight change is similar, except the changes occur ~10 years later in life. Lean body weight (primarily skeletal muscle) begins to decline by middle age as a result of many factors, including decreasing exercise and age-related declines in hormones (eg, testosterone, estrogen, and growth factors), metabolism, alpha motor units in the spinal column, and muscle protein synthesis. It should be noted also that muscle mass in older adults can rapidly decline with even brief periods of bed rest. Fat mass increases until 60–70 years of age before gradually declining. Even when there is no change in total body weight, total fat mass tends to increase as lean body mass declines. Much of this fat gain occurs within the abdomen (visceral fat) and in the subcutaneous tissue of the torso, and this process accelerates after age 65. Bone mass declines in both older men and women. However, there is an accelerated loss of bone in women in the years after menopause.

Daily energy requirements decline with age, even during healthy aging. The primary reason for this decrease is the loss of muscle mass, which is much more metabolically active than fat tissue. Another cause is a decrease in physical activity.

Older adults have a reduced ability to regulate food intake. They are much less likely, compared with younger persons, to normalize their nutrient intake after either over- or undereating. Thus, appetite can remain poor for an extended period after illness-caused low food intake.

In some settings, such as the intensive care unit, indirect calorimetry is probably the optimal method of determining caloric requirements. In most cases, however, any one of several formulas (Table 38-1) can be used to estimate resting caloric needs. A “middle of the night ” quick estimate is 30 kcal (126 kJ)/kg/day. All of these estimations require adjustment for activity level and illness severity; further adjustments depend on change in body weight and clinical response. It is important to not overfeed (see discussion of overfeeding syndrome).

MACRONUTRIENT REQUIREMENTS

Water

Water is often overlooked as a nutrient. Most adults need a maintenance water intake of 30 mL/kg body weight, with a minimum total daily intake of 1.5–2 L. Persons with excessive losses (eg, fever, diarrhea, hot weather) will need more. A decrease in thirst perception, decreased fluid intake in response to elevated serum osmolality, and decreased ability to concentrate urine after fluid deprivation occur in normal aging and increase the risk for dehydration. Cognitive decline, chronic disease, and decreased mobility may also impair fluid intake. Some persons deliberately restrict fluid intake in an effort to control urinary incontinence. Hospitals and nursing homes can easily become “water deserts” because of impaired access to water. The occurrence of an acute febrile illness or inadequate shelter during a heat wave can quickly lead to life-threatening dehydration. It is often necessary to actively encourage and directly observe fluid intake in bed-bound and institutionalized elderly persons. Intake and output measures are notoriously inaccurate in many clinical settings. Giving precise volume goals to caregivers and nurses, including writing fluid intake as a prescription or a formal medication order requiring documentation, is often more effective than simply asking family or staff to “push fluids.” Except in the presence of severe protein undernutrition or gastrointestinal bleeding, blood urea nitrogen levels can be used as a guide to detect dehydration and subsequent response to rehydration. “Tenting” of skin is not a specific or sensitive sign of dehydration in older adults.

To treat or prevent dehydration, cooperative adults with an acute illness should be encouraged to drink fluids until their urine is nearly colorless. If a patient is not able to consume adequate amounts of fluid orally, hypodermoclysis (clysis) is a useful alternative to intravenous (IV) hydration or hospitalization for frail older

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adults, especially in a nursing home. Insertion of a clysis needle into the subcutaneous space of the back or abdomen requires minimal training and is not as difficult to perform or maintain as an IV. Although not an acceptable route to supply medications or antibiotics, clysis is often adequate to meet fluid needs. In a frail nursing home resident who has stopped drinking because of an acute reversible event such as an infection, clysis may prevent the need for hospitalization during the period before antibiotics or other therapies take effect. Table 38-2 lists tips for improving hydration in older adults.

Table 38-1. Estimation of daily resting caloric (kcal) requirements.

Harris-Benedict equations

Males
   66 + 13.7W + 5H - 6.8A
Females
   655 + 9.6W + 1.7H - 4.7A

World Health Organization equations

Males
   13.5 W + 487
Females
   10.5W + 596

A, age in years; H, height in centimeters; W, weight in kilograms.

Dasgupta M et al: Subcutaneous fluid infusion in a long-term care setting. J Am Geriatr Soc 2000;48:795. [PMID: 10894319]

Protein

Protein requirements for older adults are 1.00-1.25 g/kg/day, a bit higher than for younger adults. Protein requirements are influenced by age, activity level, medications, nonprotein content of the diet, and health status. Caloric intake is particularly important because protein requirements to maintain nitrogen balance increase as total energy intake decreases. Protein requirements also increase with higher levels of physical activity. Corticosteroids, bed rest, injury, infection, and inflammation increase the risk of negative nitrogen balance, which can lead to rapid loss of lean body mass, primarily skeletal muscle. Older hospitalized persons who are very ill or recovering from trauma or major surgery may require ≥ 1.5 g/kg/day of protein to maintain nitrogen balance. Adequate protein intake becomes more challenging in medical conditions requiring protein restriction, such as liver or renal disease. In these situations, patients and families have to work closely with dietitians to avoid undernutrition. Increasing muscular resistance exercise when a lower intake of protein is medically required may improve nitrogen balance.

Table 38-2. Ways to improve hydration in older adults.

Round with beverage cart offering a variety of liquids.
Offer a midafternoon social snack time.
Provide alternatives, such as Jello, popsicles, health shakes, ice cream, etc.
Try inventive thickening agents like yogurt or pudding mix.
Increase the amount of fluid given with medications.
Remind the patient throughout the day to drink.

Campbell WW et al: Increased protein requirements in elderly people: new data and retrospective reassessments. Am J Clin Nutr 1994;60:501. [PMID: 8092084]

Fat

Serum lipid levels remain as strong a predictor of risk for coronary heart disease in older adults as in middle-aged adults. Very low-fat (≤ 10% of total calories) vegetarian diets have been shown to reverse narrowing within coronary arteries in persons with preexisting coronary artery disease. The dietary restriction required to adhere to this type of diet, however, makes it impractical for most people. Most current recommendations for a healthy diet suggest a diet of 25-30% of total calories coming from fat (American diets frequently have ≥ 40%) and ≤ 300 mg/day of cholesterol). Studies of diet and cardiovascular disease show a small reduction in cardiovascular events and cardiovascular mortality (with little effect on total mortality) when dietary fat intake is reduced or modified. However, this effect was only seen in trials of at least 2 years' duration. It is not clear whether a modified fat diet adds further vascular protection when older adults attain adequate lipid lowering with medications.

Fat in the diet is required for the absorption of fat-soluble vitamins (A, D, E, K). In addition, essential fatty acids must be consumed because they cannot be synthesized in the body. There 2 general categories of essential fatty acids. The omega-6 type, which are generally plentiful in the American diet, have proinflammatory properties and are the substrate for arachidonic acid, prostaglandins, thromboxanes, and leukotrienes. The omega-3 type, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and prostacyclin, decrease platelet aggregation and vasoconstriction and have anti-inflammatory properties. Per gram, fat has more than twice the calories (9 kcal) than protein or carbohydrates (4 kcal).

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Current consensus is that some fats can be particularly cardioprotective, whereas high intakes of others may be harmful. Vegetable oils (particularly flaxseed/linseed, olive, and canola) and nuts (almonds, cashews, hazelnuts, macadamia nuts, pecans, pistachios, walnuts, and legume peanuts) are rich in polyunsaturated and monounsaturated fats (flaxseed/linseed is especially high in omega-3 essential fatty acids) and appear to have particularly healthful properties. Another important source of omega-3 fat is from fatty fish, particularly salmon, mackerel, and albacore tuna. Omega-3 oils can decrease cytokine-mediated inflammation and may play a role in the management of chronic inflammatory diseases such as rheumatoid arthritis. Consuming nuts more than 5 times a week (1 oz = 1 serving) has been shown to reduce coronary heart disease risk by 25- 39%, even in very elderly persons and individuals with coronary disease. Saturated fat and partially hydrogenated fats (also called trans fatty acids) can increase total cholesterol and low-density lipoprotein (LDL) cholesterol levels and may even lower HDL cholesterol levels. Intake of these types of fat should be minimized.

Based on current data, in nonfrail adults of all ages, fat intake should not exceed 30% of total calories consumed, polyunsaturated and monounsaturated fats should predominate, and saturated fat and partially hydrogenated fat intake should be reduced. In contrast, in the frail older adult at high risk for weight loss, fat intake of all types can be encouraged to increase total calorie intake before transitioning to the healthier fats.

Harper CR, Jacobson TA: The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease. Arch Intern Med 2001;161:2185. [PMID: 11575974]

Carbohydrate

Carbohydrate requirements are generally calculated by default after determining total caloric, fat, and protein requirements. Thus, carbohydrates generally make up about 55% of total caloric intake. On very low-calorie diets, energy requirements are met by the incomplete oxidation of fatty acids, which leads to ketosis and anorexia. To prevent ketosis, at least 50-100 g of carbohydrates should be consumed daily. Unrefined, whole-grain products should be emphasized, with decreased intake of simple sugars. Eating foods with a lower glycemic index (ie, foods that are more slowly digested and absorbed and thus cause a slower rise in blood sugar and lower insulin response) may also be beneficial. Fiber is also a beneficial property of unrefined carbohydrates (see Fiber section).

Ludwig DS: The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287:2414. [PMID: 11988062]

Sodium

Whether sodium intake plays a clinically significant role in causing diseases of older adults, like hypertension, remains controversial. Most Americans, however, consume far more sodium (3.5 g/day on average) than needed for optimum health. However, many older adults find low-salt diets unpalatable. Indiscriminately recommending that all older adults be on a low-salt diet may cause more undernutrition than benefit.

Among healthy middle-aged adults (with and without hypertension), a diet rich in fruits and vegetables and low fat dairy products has been shown to significantly reduce blood pressure compared with a typical Western diet, and additional sodium restriction further reduces blood pressure in a dose-response manner. It is not known whether these results can be extrapolated to older adults. However, as long as food intake remains good, moderating sodium intake may be beneficial for both hypertensive and nonhypertensive older adults, especially those who are overweight or with a family history of hypertension. Persons with poorly controlled congestive heart failure also may require moderation of sodium consumption. Increased potassium and calcium intake may reduce blood pressure, but no specific recommendations are available.

Sodium chloride (table salt) is the most common source of sodium in the diet. One level teaspoon of table salt contains ~2.3 g of sodium. Therefore, it does not take much salt or salty foods to exceed the restrictions imposed by a low-salt (eg, 2 g sodium) diet. Most canned foods (eg, meats, soups, vegetables) and commercial snack foods contain added salt; elders are advised to read food labels carefully, particularly the number of servings per container.

Fiber

Dietary fiber (including, eg, nonstarch polysaccharides, oligosaccharides, lignin, gum, pectin) is the portion of edible material, most commonly from plants, that is poorly digested in and absorbed from the small intestine but which may undergo bacterial fermentation in the large intestine. Although it is generally recommended that people consume a diet containing 25-35 g of fiber each day, the average American diet contains only 10-15 g. A higher intake of fiber is associated with improved bowel function and is associated epidemiologically with a decreased risk for cardiovascular disease, diverticular disease, and diabetes mellitus type 2. It is unclear whether it is fiber itself or other phytochemicals and minerals associated with fiber-rich foods that may be most important. The purported beneficial effect in preventing colon cancer has been seriously questioned by studies that have shown no effect of either a wheat-bran-fiber

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supplement or a low-fat, high-fruit, high-vegetable, and high-fiber diet in reducing the recurrence of adenomatous polyps.

Insoluble fiber (eg, fruits, vegetables, and legumes) is incompletely or poorly fermented and improves colonic health by increasing fecal weight, reducing transit time, and improving laxation. Accompanying reduction in intracolonic pressure may lower the risk for diverticular disease. Soluble fiber (eg, oat and rice bran, barley, psyllium, legumes and vegetables, and modified celluloses such as carboxymethylcellulose) decreases total serum cholesterol and LDL-high-density lipoprotein (HDL) cholesterol ratios, reducing cardiovascular disease risk. It also slows stomach emptying and intestinal absorption, which can decrease blood glucose concentrations and insulin levels. Fermentation of fiber in the colon leads to gas production but also produces short-chain fatty acids that provide local nutrition to bowel mucosa, maintaining bowel wall integrity and decreasing bacterial translocation. High fiber intakes can decrease absorption of minerals like calcium, zinc, iron, and copper primarily because of the phytic content of cereals and fruits, but it still appears that the beneficial effects of fiber far outweigh potential side effects.

A diet rich in fruits, vegetables, and whole-grain foods is recommended to increase fiber intake. Most fruits and vegetables contain ≤ 2 g fiber/serving; thus, the U.S. Department of Agriculture (USDA) food guide pyramid recommends 2-3 servings of fruit, 3-4 vegetables, and ≥ 6 servings of grains each day. In considering commercial foods, purchasers are advised to look for whole grain as the first ingredient. If the first ingredient is enriched flour, it is not whole grain and contains very little natural fiber. Supplementing the diet with commercially available concentrated fiber sources may be necessary when fiber intake from natural sources is inadequate. Fiber intake should be increased gradually to avoid bloating, excess flatus, and general discomfort. Adequate fluid intake is also needed, particularly with bed-bound or inactive persons, because constipation may actually worsen.

FAILURE TO THRIVE & UNDERNUTRITION

Failure to thrive (FTT) is a commonly used but vague term that describes a deteriorating state characterized by weight loss (usually with muscle loss, or sarcopenia) and an associated loss of functional and psychological independence. Another commonly used term, cachexia (meaning “poor condition” in Greek), has been defined as the accelerated loss of skeletal muscle in the presence of a chronic inflammatory response; cachexia may occur without anorexia. As with many geriatric syndromes, causes of FTT are likely to be multifactorial. It may be precipitated following a sentinel event (such as an acute illness or hip fracture) superimposed on a background of comorbid illness and age-associated changes, or it may occur more gradually. Some of the possible contributing factors include hormonal changes in estrogen, androgens, and growth hormone; cytokines with known catabolic properties (such as interleukin-1 and tumor necrosis factor [TNF]); changes in trophic signals from the brain to muscle; decreased alpha motor neurons and changes in the neuromuscular junction; and decreased ability of muscle to protect itself from free radical stressors. Extrinsic factors include the interaction between physical activity and muscle and weight loss. Many diverse diseases, like cancer, AIDS, congestive heart failure, rheumatoid arthritis, tuberculosis, chronic obstructive pulmonary disease, and Crohn's disease, can lead to FTT, sarcopenia, and weight loss. Animal studies have shown that loss of skeletal muscle in cachexia exceeds the muscle loss as a result of simple starvation alone. As might be expected, increased nutritional support by itself has little effect on the course of FTT as long as the underlying causes persist.

Depression and dementia can lead to FTT by several pathways. They can cause both decreased appetite and increased disability, each independently resulting in malnutrition. Certain antidepressants are more likely associated with anorexia than others. Tricyclic antidepressants and mirtazapine are more likely to cause weight gain, whereas the selective serotonergic reuptake inhibitors (SSRIs), particularly fluoxetine, and bupropion have an increased association with weight loss (see Chapter 14: Depression & Other Mental Health Issues). The acetylcholinesterase inhibitors for dementia may be associated with gastrointestinal discomfort or diarrhea in some patients (see Chapter 11: Cognitive Impairment & Dementia). Because each patient's particular response to these medications is different, it is wise to monitor appetite and weight closely whenever any new medication is started, so that malnutrition can be quickly recognized and the drug stopped or changed.

Caregiving and care receiving can be associated with adverse emotional and physical effects that increase risk for FTT. Functional disability is more strongly associated with depression than age. As dependency on others escalates, the individual's sense of control diminishes. Elders living in the homes of children or grandchildren have lower satisfaction and morale than those in other living arrangements. Female caregivers rate their levels of caregiver stress and physical health as poorer than similar women not providing care, and daughters providing care are at higher risk of stress and burnout than are sons. The emotional impact on caregivers may include anger, disruption of family relationships, guilt, no time for family or self, frustration, and despair.

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In-home assessments may lead to recommendations that increase independence and reduce caregiving burden. Failing elders are associated with overstressed caregivers.

Chronic inflammation often plays an important role in FTT and cachexia. Effects include hepatic synthesis of many types of proteins, including opsonins, protease inhibitors, complement factors, C-reactive protein, and fibrinogen. The large quantities of proteins required as liver feedstock for synthesis come from skeletal muscle catabolism. Synthesis of other proteins, like albumin and prealbumin (transthyretin), is greatly reduced. Negative nitrogen balance occurs and weight loss commonly results. Fat metabolism is also affected in this inflammatory process: Lipolysis increases and lipogenesis decreases; triglyceride levels and very low-density lipoproteins increase; and lipoprotein lipase, high-density lipoprotein, and total cholesterol decrease. There is an increase in release of free fatty acids from adipose stores. Changes in carbohydrate metabolism include hyperinsulinemia, peripheral insulin resistance (redirecting glucose to the liver and away from skeletal muscle), and glucose intolerance. Hypermetabolism with an increased resting energy expenditure (REE) occurs in cachexia, unlike uncomplicated starvation. The apathy, malaise, and fatigue associated with cachexia cause a decrease in voluntary energy expenditure but do not balance the increased REE and decreased caloric intake.

Cytokines are protein mediators that regulate the acute-phase response and cachexia. The best studied of the proinflammatory cytokines are TNF-α (also called cachectin), interleukin (IL)-1, and IL-6. Some of the nutritional effects of various cytokines include anorexia, altered gastric emptying, decreased intestinal blood flow, and changes in small bowel motility. The presence of inflammatory markers in the blood of even high-functioning older adults has been found to correlate with subsequent morbidity and mortality. Table 38-3 summarizes common causes of weight loss in older adults.

Kotler DP: Cachexia. Ann Intern Med 2000;133:622. [PMID: 11033592]

Roubenoff R, Harris TB: Failure to thrive, sarcopenia, and functional decline in the elderly. Clin Geriatr Med 1997;13:613. [PMID: 9354744]

PROTEIN-ENERGY MALNUTRITION

Protein-energy malnutrition (PEM; the inadequate intake of protein and calories) or undernutrition is common. Unintentional weight loss is found in up to 13% of elderly outpatients and in 30-80% of nursing home residents. Usual aging is commonly associated with increasing risk for acute illness, chronic illness, and subsequent medication use, all of which can contribute to anorexia. Other mediators of anorexia include cytokines (see Failure to Thrive & Undernutritionsection), humoral factors (bombesin-like substances, cholecystokinin), and possible anorectic agents like corticotropin-releasing factor. Common causes for weight loss in older adults are listed in Table 38-3.

Table 38-3. Causes of poor food intake & failure to thrive in older adults.a

Social/psychological
      Isolation, loss of social meal setting, emotional isolation
      Depression, bereavement, grief
      Unable to drive or walk to the market
      Alcohol abuse (often hidden)
      “Instant bachelors” who have never learned to buy, store, or prepare food
      Finicky eaters
      Elder abuse and neglect
      Inadequate assistance with eating
      Poverty
Physical
      Cancer
      Medications (prescription and nonprescription): digoxin, selective serotonin reuptake inhibitor antidepressants, antacids, laxative abuse, diuretics, NSAIDs, chemotherapy, anticonvulsants, antibiotics, any drug causing delirium
      Decreased sensory pleasure (decreased olfaction and taste)
      Dentures, painful, poorly fitting, absent
      Poor dental health
      Xerostomia
      Physical handicaps and decreased mobility
      Neurological impairments of chewing and swallowing (eg, stroke, dementia, Parkinson's disease)
      Memory and attention disorders (eg, dementia, psychosis)
      Chronic disease interfering with eating: chronic obstructive pulmonary disease, congestive heart failure, renal failure)
      Infections (eg, TB, AIDS, chronic low-grade aspiration)
      Metabolic disorders (eg, diabetes mellitus, hyper- or hypothroidism)
      Atrophic gastritis with decreased stomach acid
      Peptic ulcer disease
      Inflammatory bowel disease
      Intestinal motility disorders (eg, gastroparesis, constipation)
Negative reinforcers of food intake:hiatal hernia, esophageal reflux, lactose intolerance, exertional hypoxia, intestinal angina (mesenteric ischemia)

Often more than one cause is present.
NSAIDs, nonsteroidal anti-inflammatory drugs; TB, tuberculosis.

In response to energy deprivation, the body reduces its metabolic rate in individual tissues and catabolizes

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skeletal muscle, while relatively sparing viscera (liver, kidneys, gastrointestinal tract) and blood and immune tissue. This allows the body to compensate for the reduced energy intake. The cost is reduced muscle mass (including heart and respiratory muscle mass) and a decline in functional capacity, resulting in weakness and disability. Factors that prevent successful adaptation to uncomplicated PEM include severe prolonged starvation, micronutrient deficiencies, and onset of catabolic, cytokine-mediated stress (such as infection).

PEM is poorly recognized for many reasons. Early signs and symptoms are nonspecific, mimic usual aging, and often progress slowly. Appetite may decline so slowly that it is not recognized. There is no single gold standard for diagnosing PEM, although weight loss may be the most obvious characteristic to identify. The most common definition of weight loss that cannot be ignored and that must be recognized and addressed is weight loss of 5% in 1 mo, 7% in 3 mo, or 10% over 6 mo. However, more gradual weight loss, especially involuntary weight loss, such as 5% over 6-12 mo is also associated with higher morbidity and mortality. Weight fluctuations associated with fluid changes, such as during treatment for and exacerbations of congestive heart failure, may hide real weight loss. It may be necessary to measure weight more frequently to detect trends, but weighing accuracy in many health care settings is notoriously bad. Workers who weigh frail older adults should be trained and positively reinforced to weigh patients correctly and consistently (using the same amount of clothing, at about the same time of day and relation to meals, and noting the presence or absence of casts, braces, and so on) using calibrated scales. It is very helpful to have a system in place to automatically reweigh a patient if variation of ≥ 5 lbs (2.3 kg) from the previous weight is found. Patients whose weights are most critical to know, unfortunately, are frequently the most problematic to weigh; wheelchair, bed, or lift scales are available for nonambulatory persons.

ASSESSMENT OF NUTRITIONAL STATUS

Anthropometrics

Body weight is the most important anthropometric measurement of nutritional status. Body mass index (BMI) (Table 38-4) is a way of describing weight in relationship to height; that is, taller persons should weigh more than shorter persons. In persons who are not unusually muscular, an elevated BMI correlates fairly well with obesity. However, BMI does not identify persons who have replaced muscle mass with adipose tissue, nor does it distinguish persons with central obesity. As a general guide, healthier weights in younger adults are between BMIs of 20-25 kg/m2. A BMI of 25-30 is considered overweight and ≥ 30 is obese (see Obesity in Older Adults section). A BMI ≤ 20 is not necessarily harmful, but many Americans with a BMI ≤ 20 are smokers or have chronic illness or cancer that lowers life expectancy, and older persons with low BMIs have poorer outcomes when they have a serious illness than average-weight or heavier persons.

Table 38-4. Body mass index (BMI).

BMI = (weight in kg)/(height in m)2 = (weight in lbs) × 706/(height in inches)2

A variety of other anthropometrics have limited clinical applicability. These have been proposed because adiposity in certain body sites may be more harmful than in others. It has been suggested that central obesity (ie, fat within and around the abdomen) is metabolized differently and has more harmful health consequences than fat located more peripherally (ie, around the hips). It has been proposed that waist circumferences may help identify persons at higher risk (see Obesity in Older Adults section). Skinfold measurements using calipers are prone to many measurement errors and remain primarily a research tool. Bioelectric impedance may prove a better way to assess body composition.

Laboratory Assessment

The initial laboratory assessment of weight loss should include a complete blood count, glucose, electrolytes, renal and liver function, thyroid-stimulating hormone level, urinalysis, and chest x-ray film.

Although serum albumin is commonly ordered to assess protein nutrition or status, serum albumin levels have poor sensitivity and specificity as a measure of nutritional health. Albumin concentration may increase in response to corticosteroids, insulin, and dehydration; levels decrease with hydration, liver and renal disease, malabsorption, and change from an upright to a supine position and in response to inflammatory cytokines. The patient who is undergoing slow, uncomplicated starvation may maintain a near-normal serum albumin until near death by catabolizing muscle stores, reducing metabolic activity, and decreasing protein synthesis and degradation; one can die of starvation with a normal albumin. In contrast, acute and severe injury, even in a well-nourished person, often quickly causes a drop in albumin. The half-life of albumin is ~ weeks. Levels respond slowly to renutrition alone and may never normalize if inflammation is ongoing. Raising the serum albumin with intravenous albumin replacement does not improve prognosis. However, measurement of

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serum albumin does have clinical value: A low serum albumin, although not a good indicator of nutritional status, may be a powerful predictor of illness severity and mortality.

Other serum proteins have been used as nutritional markers. There are drawbacks to using serum transferrin as a nutritional marker because levels are also affected by many nonnutritional factors. Serum cholesterol < 160 mg/dL is a marker for increased risk of morbidity and mortality but not a good measure of nutrition. Prealbumin (transthyretin) has a short half-life of 2-3 days and is, like albumin, a negative acute-phase reactant. A low level can be used to confirm the clinical impression of poor nutritional status in the absence of inflammation. A progressively rising prealbumin level may help to confirm improving nutritional status; however, the clinical exam remains the best indicator (eg, the patient is getting stronger, wounds are healing, appetite is improving). Failure of prealbumin to rise when one is assured that the patient is receiving calculated amounts of nutrition (remember that patients often do not receive the nutritional intake that is medically ordered because of, eg, delirium, anorexia, delayed initiation of feedings, procedures that require feedings to be held, accidental enteral tube removal, or feeding intolerance) should prompt a clinical workup for an occult catabolic or inflammatory process.

Fuhrman MP: The albumin-nutrition connection: separating myth from fact. Nutrition 2002;18:199. [PMID: 11844655]

Sullivan DH: What do the serum proteins tell us about our elderly patients? J Gerontol Med Sci 2001;56:M71. [PMID: 11213278]

Clinical Assessment

A comprehensive clinical assessment of nutritional status is the most useful way to identify undernutrition, and several assessment instruments exist. One

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tool is the Subjective Global Assessment (Figure 38-1). Another tool is the Mini-Nutritional Assessment (Figure 38-2). These tools show promise but have not been rigorously studied in large and varied geriatric populations.

 

Figure 38-1. Subjective Global Assessment (SGA).

Dietary Assessment

How much is the patient eating and drinking? What seems an easy question is frequently difficult to determine accurately. Accurate calorie counts can be invaluable but are frequently very difficult to obtain. At home, over several days patients or their family can fill out a food diary, which a dietitian can then interpret. There are many barriers to constructing an accurate diary, among them dementia, delirium, psychiatric illness, benign forgetfulness, and illiteracy. Calorie counts in inpatient settings are also frequently inaccurate. Some reasons for this include inaccurate estimations of food consumption by nursing or dietary personnel, misplacement of written estimates, food on meal trays being eaten by other patients or family members, food brought in from the outside that is not recorded, and tube feedings that are stopped and restarted sporadically. Nursing aides can be a valuable resource when asked about global food intake or aversive behaviors in their patients.

Vellas B et al: Nutrition assessment in the elderly. Curr Opin Clin Nutr Metab Care 2001;4:5. [PMID: 11122552]

TREATING UNDERNUTRITION

Once treatment is begun, an organized strategy for periodic reassessment is mandatory to ensure that the patient's nutritional status is improving. If the patient is not improving, appropriate reevaluations must be been done and alternative interventions attempted.

Bouras EP et al: Rational approach to patients with unintentional weight loss. Mayo Clin Proc 2001;76:923. [PMID: 11560304]

Behavioral Interventions for Poor Food Intake

Table 38-5 lists some approaches for improving dietary intake in older adults. Eating is the most social of the activities of daily living, the first one mastered as a child and often the last lost in old age. Patients often eat better, and more, when fed by family members. One reason for this is the length of time the family member dedicates to unhurriedly feeding and encouraging the patient. Successfully motivating anorexic persons to eat requires a multidimensional approach, including treating pain, increasing social supports, identifying realistic goals (eg, being able to care for oneself or being able to return home), encouraging the hope of getting stronger, and adapting to individual food preferences and meal times. Exercise as simple as daily walking may improve appetite in some patients. Refusal to eat or swallow should not be attributed to a voluntary “death wish” until the patient has undergone a detailed psychiatric assessment and been given appropriate treatment for possible depression.

Oral Supplements

A variety of commercial liquid and powder supplements can be used when patients are unable or unwilling to consume enough regular food. Nutritional supplements are most effective when consumed between meals so patients do not substitute supplement intake for regular meals. However, because of the necessary staff and time demands, between-meal consumption is rarely accomplished. It is common to see unopened canned supplements stacked on patients' bedside tables. Some patients consume these readily and eventually transition back to a regular diet; others, however, find them unpalatable. Powder formulations allow the supplement to be masked by mixing it with other food. A major barrier to the canned supplements is cost, even with generic brands. For patients with no history of lactose intolerance, instant breakfast powders mixed in milk are a satisfactory and less expensive alternative. When calculating water intake, canned protein supplements contain ~70% water. The role for nutritional supplements in healing pressure sores remains uncertain. Supplements targeted to specific patient populations (eg, renal failure, posttrauma, or ventilator dependent) may be useful, though at increased cost.

Potter JM: Oral supplements in the elderly. Curr Opin Clin Nutr Metab Care 2001;4:21. [PMID: 11122555]

Agents to Stimulate Appetite & Promote Weight Gain

A variety of medications have been promoted as helping to improve appetite and increase weight; however, none has proven satisfactory among the elderly. The progestational agent megestrol acetate has been shown to increase appetite and weight in AIDS patients and was found to improve morbidity in frail older adults after it was discontinued. Recent studies of the drug have shown that gained weight tends to be in adipose tissue, whereas skeletal muscle mass actually decreases. Most older adults do not tolerate the dysphoria associated with dronabinol use. Cyproheptadine has not been shown to be effective in older adults. The anabolic agents growth hormone and insulin-like growth factor are extremely expensive and associated with frequent side effects. Androgen therapy with testosterone or its analogues also has many side effects; its use for weight

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gain remains experimental. Anti-inflammatory therapies that affect arachidonic acid metabolism and cytokine release, including the omega-3 fatty acids, are also being studied. Anticatabolic agents, such as those with anticytokine activity, are still investigational.

 

Figure 38-2. The Mini Nutritional Assessment tool evaluates the risk of malnutrition in older adults. On the basis of the score, patients are divided into 3 categories: well nourished, at risk for malnutrition, and at risk for undernutrition. Several body measurements must be made, which may be difficult or may require training. From Vellas BJ et al: The Mini Nutritional Assessment: MNA. Serdi Publishing, 1994. Used with permission

Table 38-5. Methods to increase food intake in older adults.

Offer comfort foods:chicken soup, tea, ice cream, poached egg on toast.
Offer a happy hour beverage, visually appealing and nutrient dense (shakes, smoothies, coolers, etc.) in social milieu (festive tea cart, staff member's wear chef hats and aprons, beverage in punch bowl, etc.).
Encourage companionship during meal preparation and feeding.
Maximize caloric intake at favorite meal of the day.
Take medications with meals to minimize anorexia and nausea.
Increase physical activity.
Avoid constipation and diarrhea.
Reduce distractions and noise; turn off the television and radio.
Use finger food, including while walking; keep these foods visible during the day.
Give one food item at a time; clear away unnecessary items.
Offer several small meals throughout the day.

Persons with persistent anorexia may benefit from a trial of antidepressant therapy.

Artificial (Tube) Feeding

Anorexic patients will often eat more if enough time is taken to hand-feed them. If such a patient is still unable to consume adequate nutrition, the provider should discuss the risks and benefits of other nutritional interventions. If the gastrointestinal tract is functioning, it is strongly preferred to use it for nutritional delivery rather than parenteral routes. Although each state has different laws, it is not clinically mandatory to use artificial feeding when physicians, patients, and their families believe the risks and side effects outweigh the benefits (see Chapter 44: Palliative Care & Pain Management). Some clinicians initiate artificial feeding in a

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therapeutic trial for a limited and predetermined duration with the understanding that if certain goals (eg, the person will begin to voluntarily consume sufficient calories for survival) are not achieved, the intervention can be withdrawn. A 2- to 4-week trial is reasonable.

Diarrhea is common in tube-fed patients. This is frequently due to medication side effects, because sorbitol is often used as a drug solvent. The use of fiber-enriched supplements or simple antidiarrheal agents may help once it is ensured that the patient does not have liquid stool running around an impaction. When beginning tube feedings, it is useful to periodically assess stomach residuals; high residuals are associated with increased aspiration risk. Bowel motility is commonly impaired in frail bed-bound persons and after surgery. Early initiation of postoperative oral feedings does not invariably improve bowel function. Mobilization of the patient also does not, by itself, improve gastrointestinal function after surgery. Opioid medications almost always cause significant constipation. Metoclopramide may be tried to improve motility but frequently has side effects and should be used at low doses and stopped as soon as possible. Erythromycin cannot be routinely recommended to spur bowel motility.

A common reason to consider tube feeding is because of dysphagia and recurrent aspiration. When counseling patients and families about alternative feeding strategies, it is important to inform them that all tube feeding (both nasogastric and percutaneous) is associated with a significant risk for aspiration and pneumonia. Keeping the head of the bed elevated to 30° during feeding is only somewhat helpful. Maintaining a nasogastric tube in the confused patient may necessitate physical restraints and thus lead to injury and decreased quality of life. Nasogastric tubes are often accidentally pulled out and feedings disrupted. They have to be taped to the face and can cause nasal irritation or erosion. Replacing tubes requires confirmation of placement in the correct location, usually by radiography. Endoscopically placed abdominal (percutaneous endoscopic gastrostomy; PEG) tubes are usually easily maintained, but placement has some risk; these can also be pulled out by patients. If a PEG tube is dislodged, it should be replaced immediately or a catheter inserted because the tract can close quickly, requiring complicated reinsertion.

Continuous tube feeding is usually better than bolus feedings in the bed-bound patient. Nighttime tube feedings can be given if the patient does not meet a defined caloric intake during the day.

Parenteral Nutrition

Nutritional intervention is often delayed in the hopes that a patient will soon begin voluntary eating or because of barriers to artificial feeding. Peripheral parenteral hyperalimentation is easier to initiate and maintain than central hyperalimentation. It is a useful intervention when begun promptly after anticipating that oral intake is likely to be poor for several days. It continues to be underused. Maintaining some enteral nutrition, however, decreases gut mucosal atrophy and the risk of bacterial translocation and peritonitis. In general, delaying nutritional support increases morbidity.

Complication: Refeeding Syndrome

There is danger in rapidly providing large quantities of nourishment, particularly to a slowly starved but stable patient. Overfeeding a debilitated person can cause a potentially fatal refeeding syndrome. If the patient's liver and kidneys are functioning, protein intake should initially not exceed 1.5 g/kg of the patient's normal weight. The Harris-Benedict or World Health Organization (WHO) equations (see Table 38-1) can estimate initial caloric needs if indirect calorimetry is not available. The hyperglycemia associated with overfeeding leads to hyperinsulinemia, with its deleterious effects on blood vessels, and to antinatriuresis, causing fluid retention. Because the patient's heart muscle is also likely to be atrophic, with impaired ability to respond appropriately when overloaded, patients are at high risk of sudden pulmonary edema. Thus, it is important to initiate feeding at intakes of 100% to not more than 120% of the Harris-Benedict/WHO-calculated requirements and to meticulously monitor mineral and electrolyte measures (potassium, phosphate, magnesium) and cardiac status. A rising heart rate may be a subtle indicator of fluid overload. Weight gain ≥ 1 kg/week should be considered fluid retention and avoided.

Crook MA et al: The importance of the refeeding syndrome. Nutrition 2001;17:632. [PMID: 11448586]

OBESITY IN OLDER ADULTS

Aging in the United States is commonly associated with a decrease in lean body mass and a progressive increase in fat stores. This adipose tissue tends to be distributed to the abdomen, even in healthy older adults and those with no change in weight. In the United States, ~42% of men and women between the ages of 60 and 69 and 37% between the ages of 70 and 79 are overweight (BMI ≥ 25 kg/m2). Among persons older than 80, 18% of men and 26% of women are overweight. Controversy exists as to the definition of healthy weight for adults older than 70. Obesity is associated with highest mortality in young adults; it appears to have less prognostic significance in old age. Obesity in frail older adults may be protective against injury from falls or may provide a

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nutritional buffer during acute illness. On the other hand, obesity is associated with increased risk of knee and hip arthritis and decreased physical function. Elevated BMI strongly predicts risk for symptomatic knee osteoarthritis in elderly women, and weight loss significantly lowers the osteoarthritis rate in women whose BMI exceeds 25 kg/m2. Central obesity is associated with increased cardiovascular disease, diabetes mellitus, and hypertension in whites and, perhaps, black men. It has been suggested that a waist circumference ≥ 94 cm (37 in.) in men and 80 cm (31.5 in.) in women is associated with increased cardiovascular risk. However, neither BMI nor fat location seems to predict mortality in black women, except in the case of extreme obesity. Much remains to be learned about racial differences in fat patterning and its health consequences.

Aggressive weight loss should not be attempted or encouraged in most older adults. Those who are obese and have poorly controlled hypertension, diabetes mellitus, functional impairment, or lower extremity arthritis may benefit from gradual weight reduction (under close supervision to prevent malnutrition). Sustained weight loss generally requires a combination of healthy diet and exercise. Exercise does not have to be strenuous; simple walking can be extremely successful, if done regularly.

A relatively small amount of weight loss, perhaps as little as 5-10%, may significantly improve hypertensive or diabetic management. Nevertheless, involuntary weight loss in any older adult, including obese older persons, is associated with high morbidity and mortality and should not be ignored.

Micronutrients

The Recommended Dietary Allowance (RDA) is defined as the average daily intake of a vitamin or mineral that is sufficient to meet the nutrient requirements of most (98%) healthy individuals. Table 38-6 lists RDAs for selected vitamins and minerals. Persons who have medical disorders may need more or less than the RDA for healthy persons. Tolerable upper intake levels (ULs) have also been estimated for certain micronutrients. This is the upper intake that is likely to pose little risk for adverse side effects in most people. The UL allows patients and health care workers to consider possible risks if large amounts of vitamin and mineral supplements are consumed. The ideal intake of vitamins and minerals needed for optimum health may be higher than the RDAs and remains under active study.

Risks for Micronutrient Deficiency

Most persons who have macronutrient undernutrition have multiple micronutrient (vitamin and mineral) deficiencies as well. In addition, isolated micronutrient deficiencies can occur, particularly as the result of drug-nutrient interactions (Table 38-7). It is difficult to quickly and inexpensively determine micronutrient status for many vitamins and minerals. Moreover, blood micronutrient concentrations, especially those of fat-soluble vitamins and many minerals, may not accurately estimate tissue and storage pools. Micronutrients bound to plasma proteins will be affected by hypoproteinemia; in the presence of PEM or hypoalbuminemic states, ionized fractions may be more useful for assessing status for some micronutrients, such as calcium. Except for vitamin B12 and folic acid, water-soluble vitamin nutrition or status is not commonly measured, and specific vitamins are supplemented based on individual risk factors.

Table 38-6. Recommended dietary allowances (RDA) and tolerable upper limits (ULs) for selected vitamins & minerals.a

Vitamin/mineral

RDA

UL

Vitamin A (retinol)

Men: 900 µg
Women: 700 µg

3000 µg

Vitamin D

Adults < 50: 200 IU
Adults 51-70: 400 IU
Adults > 70: 600 IU

2000 IU

Vitamin E

15 mg
22 IU natural vitamin E
33 IU synthetic vitamin E

1500 IU

Vitamin K

Men: 80 µg
Women: 65 µg

b

Vitamin B1 (thiamin)

Men: 1.2 mg
Women: 1.1 mg

b

Vitamin B2 (riboflavin)

Men: 1.3 mg
Women: 1.1 mg

b

Niacin (nicotinamide)

Men: 16 mg
Women: 14 mg

b

Vitamin B6 (pyridoxine)

Men: 1.7 mg
Women: 1.3 mg

100 mg

Vitamin B12 (cobalamin)

2.4 µg

b

Folic acid (folate)

400 µg

1000 mg

Vitamin C (ascorbic acid)

Men: 90 mg
Women: 75 mg(increase by 35 mg if a smoker)

2000 mg

Calcium

1200 mg

2500 mg

Selenium

55 µg

400 µg

aThe RDA is the recommended average daily intake that will fulfill the nutritional needs of most healthy adults. The UL is the highest level of daily nutrient intake that is likely to pose no adverse health risk in most people. As intake above the UL occurs, there is an increasing risk of adverse effects.
bTolerable upper limit not yet determined.

Table 38-7. Potential drug-nutrient interactions.

Vitamin A: mineral oil, cholestyramine
Vitamin D: mineral oil, phenytoin, primidone, corticosteroids, cholestyramine
Vitamin E: warfarin (Coumadin)
Vitamin K:antibiotics
Thiamin (vitamin B1): thiamin antagonists in coffee, tea, raw fish, red cabbage, chronic alcohol abuse
Riboflavin (vitamin B2): phenothiazines
Pyridoxine (vitamin B6): levodopa, isoniazid, hydralazine, penicillamine, cycloserine
Niacin: aspirin
Folic acid: sulfasalazine, trimethoprim, phenytoin, primidone, phenobarbital, alcohol, methotrexate, triamterene, metformin, 5-fluorouracil
Vitamin B12: antacids, nitrous oxide, metformin

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Bates CJ: Diagnosis and detection of vitamin deficiencies. Br Med Bull 1999;55:643. [PMID: 10746353]

NUTRITION & IMMUNITY

Malnutrition, particularly PEM, is known to impair immune status in older adults, particularly specific B and T cell-mediated functions and nonspecific immunity (polymorphonuclear cells and monocytes). Certain vitamins also appear to have a role in immune function. Vitamin B6 supplementation causes more robust lymphocyte proliferative responses to T and B cell mitogens and increased IL-2 production in older adults. Supplementation of healthy older adults with vitamin E and beta carotene has been found to increase delayed-type hypersensitivity (DTH) responses and lymphocyte proliferation in some but not all studies. Cell-mediated immunity may also decline in folate deficiency. The evidence that ascorbic acid (vitamin C) deficiency plays a significant role in immune function or that high-dose supplementation reduces viral infections or duration of illness is weak and remains unproven. Studies examining the effect of multivitamin supplementation on immune status have produced mixed results.

Trace minerals play a role in immune function. Zinc, for example, can affect immune function, but readily available measures of tissue zinc status are not available. Serum zinc is not a good marker of tissue status; low serum zinc usually reflects an acute-phase response with hepatic sequestration and wound tissue uptake. Older adults commonly have low zinc intake, which is correlated with poor immune function and tissue healing. Supplementation with the RDA of zinc is recommended. However, high intakes (≥ 100-150 mg/day) will depress immune status and copper absorption and should not be continued for more than several weeks. Improved wound healing with high-dose zinc supplementation is not seen in zinc-sufficient patients. High zinc intake can cause abdominal discomfort and anorexia.

NUTRITION & COGNITION

The investigation of reversible causes for dementia traditionally includes the assessment of folic acid and vitamin B12 status, although the evidence to support this practice remains weak. Persons with low vitamin B12 or folic acid levels have been found to be at higher risk for Alzheimer's disease. However, although deficiency of these vitamins is common in frail older adults, vitamin B12 and folic acid supplementation rarely changes the course of slowly progressive cognitive decline. At present, any direct relationship between vitamin intake and risk of dementia remains unclear.

One of the hypotheses concerning the cause of Alzheimer's disease is that it is due to oxidative stress. Studies have suggested a potential role for antioxidants, like vitamin E, in modifying the course of Alzheimer's disease; further research will be needed before any convincing protective effect is proven. Cross-sectional data have also implicated a role for carotenoid intake in protecting against cognitive impairment, perhaps by decreasing small vessel disease in the brain.

Foley DJ, White LR: Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3261. [PMID: 12076225]

Seshadri S et al: Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346:476. [PMID: 11844848]

Vitamin B12 (Cobalamin)

Recent population studies suggest a prevalence of about 10-15% for vitamin B12 deficiency in older adults. Table 38-8 lists the most common causes of vitamin B12 deficiency. Pernicious anemia, an autoimmune disorder causing decreased gastric intrinsic factor production, is not a common cause of deficiency among elders. Cobalamin deficiency in older adults is more likely due to malabsorption of cobalamin bound within foods, often the result of atrophic gastritis and hypochlorhydria. Stomach acid helps to remove the vitamin from food and make it bioavailable. Disorders that interfere with enterohepatic absorption (such as small bowel disease or surgery) will lead to deficiency more rapidly than low intake because enterohepatic vitamin B12 recycling will be impaired, with the vitamin lost in the stool.

Vitamin B12 deficiency can present clinically with 2 relatively independent disorders. One is a hematological disorder characterized by megaloblastosis, macrocytosis,

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and anemia. A separate neurological disorder can cause peripheral neuropathy, with paresthesias and numbness; spinal column lesions, causing loss of vibration and position sense, sensory ataxia, limb weakness, orthostatic hypotension, and plantar extensor responses; and neuropsychiatric symptoms, including delirium, cognitive impairment, and depressive symptoms. Signs and symptoms of vitamin B12 deficiency are nonspecific and common in many older adults with multiple medical problems. Many patients with low vitamin B12 serum levels are asymptomatic. Current laboratory norms for vitamin B12 status are too low and do not identify patients with early deficiency. Many patients with low-normal vitamin B12 serum levels (200-350 pg/mL; 150-260 pmol/L) have measurable biochemical indicators of deficiency, including elevated methylmalonic acid (MMA) (≥ 270 nmol/L) levels, which normalize with supplementation. These apparently asymptomatic cases likely represent an early preclinical deficiency state. Renal insufficiency can also elevate MMA. Homocysteine (Hcy) elevations are less specific and are also affected by folate and vitamin B6 status; Hcy measurements are not recommended for detecting early vitamin B12deficiency.

Table 38-8. Causes of vitamin B12 deficiency.

Atrophic gastritis and hypochlorhydria
Chronic antacid use (H2 blockers, proton pump inhibitors)
Gastric surgery
Ileal surgery
Diseases of the small intestine and terminal ileum:Crohn's disease, sprue, malabsorption syndromes
Helicobacter pylori infection
Pancreatic insufficiency
Parasitic infections of small bowel (eg, fish tapeworm)
Bacterial overgrowth syndromes
Strict vegetarianism
AIDS and AIDS treatment (eg, zidovudine)
Pernicious anemia
Metformin

Table 38-9 provides an approach to screening for vitamin B12 deficiency and treatment guidelines. Intramuscular or oral replacement is most common; alternative formulations (such as nasal gels) are generally more costly and have not been rigorously tested. The practice of prescribing vitamin B12supplementation as a general tonic is not recommended.

Neurological symptoms of B12 deficiency may not improve unless therapy is begun very early. Only rarely does a progressive dementia improve in this setting. Older patients and those with more severe or long-standing symptoms appear to have worse odds of recovery.

Table 38-9. Recommendations for screening for & treating vitamin B12 deficiency in older adults.

1. Screen with a serum vitamin B12 level any older adult who is frail, has macrocytosis or neutrophil hypersegmentation with or without anemia, has peripheral neuropathy or gait disorder, or has otherwise unexplained neuropsychiatric symptoms.

2. Any patient with a vitamin B12 serum level < 200 pg/mL 150 pmol/L) can be considered deficient. A serum level between 200-350 pg/mL (150-260 pmol/L)is borderline deficient.

3. Most older adults who are deficient can be treated with supplementation without further investigation. It usually is not essential to prove that the older patient has pernicious anemia or intrinsic factor deficiency by testing for antibodies to intrinsic factor or performing a Schilling test.

4. Most older adults who are borderline deficient should also be treated. If it is necessary to obtain further biochemical evidence that a borderline serum vitamin level represents significant deficiency, an MMA level (serum or urine) can be obtained before and after treatment (an elevated MMA level should fall to normal with correct treatment).

5. All patients with possible symptoms of vitamin B12 deficiency should be supplemented parenterally. This can be accomplished by giving several intramuscular injections (1000 µg) within several days to weeks and then continuing supplementation indefinitely with monthly injections.

6. Any healthy patient whose deficiency was found incidentally and is otherwise asymptomatic can be given a trial of oral supplementation (1 mg daily). These patients should have a serum vitamin B12 level reassessed within the first month to confirm absorption and periodic (once or twice yearly) screening thereafter.

MMA, methylmalonic acid.

Folate (Folic Acid)

Folate deficiency is associated with general malnutrition and alcohol abuse and with use of folate antagonists, such as methotrexate, phenytoin, sulfasalazine, primidone, phenobarbital, and triamterene. Like vitamin B12 deficiency, it can present as a megaloblastic macrocytic anemia. Folate supplementation may improve the hematological picture in combined vitamin B12-folate deficiency states, without correcting the ongoing neurological disorder of vitamin B12deficiency. Clinicians commonly assess both vitamin B12 and folate status in any patient with macrocytosis. However, low folate intake is a very unusual cause for macrocytosis. Fortification of grains with folic acid began in the United States in 1998 in a program to reduce neural tube defects. The concern that grain fortification would mask vitamin B12 deficiency has not been proven.

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Folate deficiency appears to be associated with, and may cause, cognitive impairment. Some studies have found slowed mental processing (including poorer performance on mental status testing) and depressive symptoms in patients with folic acid deficiency. Other research has found associations between low serum folate and cerebral cortical atrophy. Epidemiological investigations point to a connection between hyperhomocysteinemia (which can result from folate deficiency) and Alzheimer's disease or vascular dementia. Ongoing studies are exploring whether vitamin supplementation can reverse or prevent cognitive decline.

Folate status may be assessed by measuring (1) serum folate if dietary intake (diet or vitamin supplementation) has not recently changed or (2) erythrocyte (red blood cell) folate if there has been a recent change in diet (as after hospital admission).

NUTRITION & VASCULAR DISEASE

Elevated levels of Hcy are associated with thrombogenicity and vascular disease throughout the body. Folic acid (and, to a lesser extent, vitamins B12 and B6) supplementation can lower Hcy levels. After fortification of grains in the United States in 1998, Hcy levels have declined in the general population. A combination of folic acid (1 mg), vitamin B12 (400 µg), and pyridoxine (10 mg) given for 6 mo to patients averaging 61 years of age after coronary angioplasty significantly reduced Hcy levels and arterial restenosis. Studies are currently underway to determine whether specific vitamin therapy will reduce clinical end points of heart attack and stroke. Consumption of a diet rich in fruits and vegetables continues to be recommended as the best source for folic acid, but folate supplements of 400-1000 µg may additionally be taken.

Antioxidants have been promoted as protective against cardiovascular disease for many years. Many epidemiological observational studies have shown a lower rate of cardiac death in people who consume a diet rich in the antioxidant vitamins E and C and carotenoids. The carotenoids in general, and beta carotene in particular, have antioxidant properties in some model systems but not in others. High levels of serum carotenoids are associated with a lower risk of periventricular white matter lesions on magnetic resonance imaging, particularly in smokers. These findings are difficult to interpret because diets rich in antioxidants are also higher in fiber and lower in cholesterol and saturated fat, and people who consume large amounts of fruits and vegetables or who take vitamin supplements often have healthier lifestyles. Randomized clinical studies for primary prevention of cardiovascular disease have not found that any single vitamin is consistently beneficial. In fact, some studies have found increased mortality with the use of beta carotene and vitamin E. Vitamin E may increase risk for hemorrhagic stroke.

Overall, the evidence to date is insufficient to conclude that antioxidant vitamin supplementation reduces clinically significant oxidative damage in humans, although large randomized in the United States and Europe are continuing.

Brown BG et al: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583. [PMID: 11757504]

Yusuf S et al: Vitamin E supplementation and cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154. [PMID: 10639540]

Hooper L et al: Dietary fat intake and prevention of cardiovascular disease: systematic review. BMJ 2001;322:757. [PMID: 11282859]

Tice JA et al: Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease. JAMA 2001;286:936. [PMID: 11509058]

NUTRITION & CANCER

In observational studies, populations who consume foods highest in antioxidants (fruits and vegetables) have lower cancer rates. It is difficult to determine whether these findings are due to the antioxidant nutrients themselves or to other healthy behaviors. Some clinical prevention trials using micronutrients have shown promising effects: selenium in lung, prostate, and colorectal cancer; beta carotene, vitamin E, and selenium in stomach cancer; and vitamin E in prostate and colon cancer. Other studies, however, have found an increased risk of cancer in some patients taking beta carotene supplements, and vitamins may impair the effectiveness of cancer therapy by protecting cancer cells during radiation therapy. Fiber intake remains unproven as a protective agent against colon polyps or cancer, but it has other benefits. Any protective role for other nutrients (vitamin D analogues; calcium; phytonutrients such as green tea, lycopene, and soy isoflavones) and general diets (eg, the Mediterranean diet) remain under investigation.

Scheppach W et al: WHO consensus statement on the role of nutrition in colorectal cancer. Eur J Cancer Prev 1999;8:57. [PMID: 10091044]

NUTRITION & AGE-RELATED EYE DISEASES

Evidence to support a protective effect of individual antioxidant vitamins on age-related eye diseases is conflicting. Zinc may have a role in preventing age-related

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macular degeneration or in slowing its progression. Critical assessment of related studies support a diet rich in antioxidants rather than vitamin supplements to possibly prevent age-related cataract. Smoking has been shown to be the strongest environmental risk factor for age-related macular disorders.

Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. Arch Ophthalmol 2001;119:1417. [PMID: 11594942]

Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss. Arch Ophthalmol 2001;119:1439. [PMID: 11594943]

NUTRITION & BONE HEALTH

Low bone density is common in older adults and is associated with hip and vertebral fractures. One common cause is osteoporosis, a multifactorial disease that causes brittle bones (see Chapter 27: Osteoporosis & Hip Fractures). Another cause is osteomalacia, resulting from vitamin D deficiency. In older adults, osteoporosis and osteomalacia frequently coexist.

Daily intake of elemental calcium should be ~1200-1500 mg in most persons after adolescence. There are a variety of calcium sources. A cup of milk or yogurt contains ~300 mg of calcium. Green vegetables contain some calcium, but they also contain other phytochemicals that interfere with calcium absorption. Therefore, calcium bioavailability from vegetables may be limited. Many persons will be unable to consistently obtain the recommended intake of calcium from natural sources and will need to take calcium supplements. Some brands of orange juice, candy, and other foods now contain added calcium. In pill form, calcium carbonate is the least expensive; absorption improves when consumed with food (although high-fiber foods may reduce absorption somewhat). Some formulations, like calcium citrate, are better absorbed but cost more. Calcium supplements can increase constipation in some individuals. Perhaps paradoxically, persons who develop calcium oxalate kidney stones should not be on a low-calcium diet because dietary calcium can bind with and reduce food oxalate absorption and thereby decrease risk of stone formation.

Vitamin D is required for calcium absorption, and vitamin D receptor density in the intestine decreases with age. The capability of the skin to manufacture vitamin D when exposed to sunlight also decreases with age and with use of sunscreens. In addition, in the winter in many parts of the United States, low sun exposure prevents significant cutaneous production of the vitamin. Thus, for various reasons, supplementation of vitamin D is often necessary for many older adults. A combined vitamin D-calcium supplement is recommended because most older adults will benefit from both. Persons taking glucocorticoids also need supplementation of calcium and vitamin D to reduce bone loss. Because of the toxicity of vitamin D, it is important not to exceed the UL of 2000 IU.

Very high intakes of vitamin A are associated with an increased incidence of hip fractures in postmenopausal women who are not taking estrogen. It is recommended that the UL for vitamin A (3000 µg) not be exceeded.

Janssen HCJP et al: Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 2002;75:611. [PMID: 11916748]

VITAMIN & MINERAL SUPPLEMENTATION

Many older adults, including those who are healthy and living independently as well as those who are frail, ill, or institutionalized, are at risk for subtle micronutrient deficiencies. Most adults do not consistently consume recommended amounts of fruits and vegetables. As aging progresses, risk factors for poor intake, adverse drug-nutrient interactions, and nutrition-related diseases increase. Many persons in the United States (currently ~40% of adults) consume supplemental vitamins. Current evidence suggests that daily intake of a vitamin-mineral supplement, supplying the RDA, can be recommended for all older adults and is associated with no significant adverse effects. It remains unclear whether intakes above the RDA are associated with significant health benefits, and high intake of some micronutrients (particularly vitamins A, D, and pyridoxine) and many minerals is well known to cause toxicity. Certain subgroups (eg, smokers, persons at risk for hemorrhagic stroke) may be at higher risk for side effects from vitamin supplementation.

Patients should be counseled not to exceed the UL (see Table 38-6), except under medical guidance, and should be reminded that improved health is directly related to modifying more clearly associated cancer and cardiovascular risk factors, such as smoking, hypertension, diabetes mellitus, saturated fat intake, and exercise. Vitamin and mineral supplementation does not substitute for healthy nutrition. Clinicians should ask about vitamin and mineral supplement use when reviewing their patients' medications lists.

Willett WC, Stampfer MJ: What vitamins should I be taking, doctor? N Engl J Med 2001;345:1819. [PMID: 11752359]