Melissa Sum and Shelby Sullivan
General Nutritional Considerations
DEFINITIONS
· Macronutrients: provide energy and consist of protein, carbohydrate, and fat.
· Micronutrients: do not provide energy and consist of vitamins and minerals.
· Essential nutrients: nutrients not synthesized by the body and therefore completely supplied by the diet.
· Malnutrition: may refer to a state of overnutrition or undernutrition. For the purposes of this chapter, will be referred to a state of undernutrition.
· Obesity: results from macronutrient overnutrition though obese patients may have micronutrient deficiencies.
· Body mass index (BMI) = weight (kg)/height2 (m2):
o Underweight: BMI <18.5 kg/m2
o Normal weight: BMI 18.5 to 25.0 kg/m2
o Overweight: BMI >25 kg/m2
o Obesity: BMI >30 kg/m2
o Morbid obesity: BMI >40 kg/m2
· A BMI outside of the normal range is associated with increased morbidity for most patients.
· Special populations may have a high BMI, but normal body fat such as athletic men or women with more muscle mass than the general population; or a normal BMI, but high body fat such as an elderly person with less muscle mass than the general population.
Dietary Guidelines
Dietary Reference Intakes
· Estimates of daily nutrient intakes that can be used for planning and assessing diets for healthy individuals.
· Consist of four reference intakes: estimated average requirement (EAR), recommended dietary allowance (RDA), tolerable upper limit (UL), and adequate intake (AI).
· Current dietary reference intakes (DRIs) can be found on the US Department of Agriculture (USDA) website.1
· EAR: estimated daily intake of essential nutrients adequate to meet the nutritional needs of 50% of the individuals in a specific age and gender group.
· RDA:
o Estimated daily intake of essential nutrients adequate to meet the nutritional needs of practically all (97% to 98%) individuals in a specific age and gender group.
o 2 standard deviations above the EAR.
o If the EAR for a given nutrient cannot be established through sufficient scientific data, the RDA for that nutrient cannot be established. When the RDA cannot be established, the AI is used instead.
· UL: The daily upper limit of intake of essential nutrients safe for most individuals. Data are lacking for many nutrients, and therefore lack of an UL does not mean that one does not exist.
· AI: The AI is used as a goal for the nutrient intake of individuals and is based on observed or experimental calculations. When sufficient data are not available to estimate an average requirement, an AI is set.
USDA Dietary Guidelines for Americans
· Developed by the USDA and the Department of Health and Human Services and revised every 5 years, most recently in 2010.
· Generally encourage Americans to eat fewer calories, to be more active, and to make wiser food choices.
· Guidelines note populations with special needs in the executive summary.
· Guidelines are the basis of the food guide plate.
· The USDA food guide plate was first released in 2011 (see Fig. 22-1). It replaced the previously used food guide pyramid that had been criticized for its lack of translatability to most Americans’ dining habits. The USDA food guide plate emphasizes the following2:
o Proportionality: shown by the division of the plate into the four nearly comparable-sized components of fruits, vegetables, protein, and grains to suggest how much food a person should choose from each group. It encourages people to make half their plate fruits and vegetables.
o Moderation: represented by the division of one plate into quarters.
o Variety: symbolized by the five colors representing the four food groups on the plate and the dairy product next to it.
· The USDA website (www.choosemyplate.gov [last accessed 1/5/15]) contains links to SuperTracker, which helps patients plan, analyze, and track their diet and physical activity to identify ways to improve. It also contains a feature that allows patients to set personal calorie goals.
Figure 22-1 United States Department of Agriculture MyPlate. (From http://www.choosemyplate.gov [last accessed 1/5/15])
Calculating Energy Requirements
· Total energy expenditure = basal metabolic rate (BMR) + the energy expenditure of activity + the thermic effect of food.
· The thermic effect of food is a small percentage of total energy expenditure and is largely ignored when energy requirements are estimated.
· Harris-Benedict equations estimate BMR on the basis of gender, height, age, and weight:
o Male: BMR (kcal) = 66.5 + (13.8 × weight in kg) + (5 × height in cm) – (6.8 × age in years).
o Female: BMR (kcal) = 655 + (9.6 × weight in kg) + (1.9 × height in cm) – (4.7 × age in years).
· Energy needs are then calculated by multiplying BMR by an activity factor between 0.8 and 1.8 that adjusts for the stress of various medical conditions and for the level of activity.
· Table 22-1 can be used for an easy reference to determine energy requirements.
TABLE 22-1 Energy Requirements Based on BMI
BMI, body mass index.
Macronutrients
Protein
· Components of protein include essential and nonessential amino acids. Essential amino acids are histidine, isoleucine, leucine, lysine, methionine/cystine, phenylalanine/tyrosine, threonine, tryptophan, and valine.
· Types of protein:
o Complete proteins contain all essential amino acids and are derived from animal sources and select plant sources such as soy, quinoa, spirulina, buckwheat, hemp seed, and amaranth.
o Incomplete proteins do not contain all essential amino acids.
· Sources of protein include meat, dairy products other than cream and butter, and plant products such as grains, legumes, and vegetables.
· Plant proteins can be ingested in combination so that their amino acid patterns become complementary. Vegans can meet requirements when grains, legumes, and leafy greens are combined.
· The RDA for protein intake in young healthy adults of both sexes is 0.8 g/kg body weight/day. The average American’s daily protein intake far exceeds the RDA.
· Protein requirements increase during growth, pregnancy, lactation, and rehabilitation.
Carbohydrates
· Carbohydrates are composed of saccharide units.
· Types of carbohydrates:
o Complex carbohydrates: polysaccharides, starch, which is digestible, and fiber, which is indigestible.
o Sugars: monosaccharides (glucose, fructose), disaccharides (sucrose, lactose, maltose), or oligosaccharides; sucrose and lactose are the primary dietary sugars.
· Carbohydrates typically comprise 45% to 65% total daily calories.
· Fiber:
o Fiber is found in all plant sources (whole grains, legumes, and prunes are very good sources) and is commercially available in sources such as psyllium (e.g., Metamucil) and methylcellulose (e.g., Citrucel).
o Fiber intake for males is 30 to 38 g/day and for females is 21 to 29 g/day.
o Most Americans do not consume the recommended amount of fiber and may benefit from supplementation.
o Soluble fiber is soluble in water and fermentable by intestinal bacteria. Pectin, gum, mucilages, and some hemicelluloses are considered soluble fibers. Benefits of soluble fiber include the following:
§ Delayed gastric emptying, slowed intestinal transit, and decreased glucose absorption with benefits in obese patients
§ Improvement in glycemic control in diabetic patients
§ A decrease in luminal wall tension (pain and cramps) and diarrhea in irritable bowel syndrome
§ Binding of fatty acids, cholesterol, and bile acids leading to lower serum lipid levels and atherosclerosis prevention
o Insoluble fiber is insoluble in water and not fermented by intestinal bacteria. Cellulose, lignin, and some hemicelluloses are considered insoluble fibers. Sources of insoluble fiber include certain plant sources (whole grains, flax seed, and certain vegetables such as celery, potato skin, and green beans). Benefits of insoluble fiber include the following:
§ Increased intestinal transit and increased fecal bulk, resulting in a laxative effect
§ May reduce the rates of diverticulosis and colonic neoplasms
Fat
· Components of fat include glycerol backbone with three fatty acid chains. Fats are categorized by the following:
o Fatty acid chain length: short-chain, medium-chain, and long-chain fatty acids.
o Degree of hydrogen saturation of the fatty acid chains: polyunsaturated (multiple unsaturated sites), monounsaturated (a single unsaturated site), and saturated (completely saturated).
o Ability of the body to synthesize the fat: essential or nonessential. Essential fatty acids are omega-3 α-linolenic acid and omega-6 linolenic acid. All other fatty acids are nonessential.
· Increasing saturation is associated with increasing risk of coronary artery disease. Unsaturated fatty acids may be hydrogenated to form trans fats.
· Polyunsaturated fats are divided into n–6 and n–3 fatty acids according to their molecular structure. A high ratio of n–6 fatty acid to n–3 fatty acid intake may be atherogenic.
· Fat should comprise no more than 35% of total daily calories, and saturated fat should comprise no more than 7% of total daily calories.
· Trans fats are made by hydrogenating vegetable oils, which solidifies the oils and increases the shelf life and flavor of the foods that contain them. They contribute to increased blood low-density lipoprotein (LDL) cholesterol, decreased blood high-density lipoprotein (HDL) cholesterol, and coronary artery disease. Trans fat should comprise no more than 1% of total daily calories.
· Monounsaturated fats (when substituted for saturated fat) have beneficial effects on the cholesterol profile decreasing LDL and triglyceride levels while increasing HDL.
Cholesterol
· Dietary fats and cholesterol are packaged into lipoproteins for delivery to the tissues.
· The classification of lipoproteins can be found in Chapter 11.
· LDL, very–low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and chylomicrons carry cholesterol to the tissues with LDL carrying 70% of serum cholesterol.
· HDL returns cholesterol from the tissues to the liver and carries 20% to 30% of serum cholesterol. HDL levels are inversely correlated with the risk of heart disease.
· Reduced saturated fat, trans fat, and cholesterol intake; weight loss; and dietary adjuncts such as soluble fiber, plant sterols and stanols, and soy protein may decrease LDL cholesterol levels.
· Aerobic exercise, weight loss through decreasing caloric intake, smoking cessation, omega-3 fatty acid intake, increased soluble fiber intake, and drinking one to two servings of alcohol daily have been associated with increased HDL levels.3
· Cholesterol intake should be <300 mg/day (Table 22-2).
TABLE 22-2 Dietary Sources of Fats
Alcohol
· Alcohol is structurally similar to carbohydrates.
· Each gram of ethanol yields 7 kcal and can be a significant source of empty calories.
· The alcohol contents in one 1.5-oz shot of hard liquor, one 12-oz beer, and one 5-oz glass of wine are roughly equivalent. One serving of an alcoholic beverage provides 14 to 20 g ethanol (100 to 140 calories) plus additional calories found in additives such as cream, sodas, or fruit juices.
· Ethanol is known to increase HDL in serum; thus, moderate ethanol use may convey a cardioprotective effect.
· Alcohol interferes with thiamine absorption and formation of its active metabolite.
Macronutrient Substitutes
· Artificial sweeteners and sugar substitutes provide sweetness with a reduction in calories. Five artificial sweeteners have been approved by the U.S. Food and Drug Administration (FDA): saccharin, aspartame, acesulfame, sucralose, and neotame (Table 22-3).
· The fat replacement olestra is a mixture of hexa-, hepta-, and octaesters of sucrose with long-chain fatty acids.
o Olestra imparts taste indistinguishable from fat yet is too large to be absorbed.
o It is currently found primarily in snack foods such as chips.
o Side effects include cramping, flatulence, and diarrhea from fat malabsorption. Poor absorption of fat-soluble vitamins may occur because they are excreted with olestra.
TABLE 22-3 Current Artificial Sweeteners
aAs compared to sucrose.FDA, Food and Drug Administration.
Micronutrients
· Vitamins are essential organic compounds that are required to maintain growth, metabolism, and overall health. Vitamins are either fat soluble (vitamins A, D, E, and K) or water soluble (all other vitamins) (Table 22-4).
· Dietary minerals are inorganic compounds that do not supply energy (Table 22-5). They are important in regulating metabolism, tissue catabolism, and anabolism, including
o Cellular regulation and fluid balance
o Coenzymes and cofactors
o Bone and tooth formation
TABLE 22-4 Water- and Fat-Soluble Vitamins
CHF, congestive heart failure; FOBT, fecal occult blood testing; NAD, nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; PUD, peptic ulcer disease; TCA, tricarboxylic acid; UA, uric acid.
TABLE 22-5 Minerals
ATP, adenosine triphosphate; CNS, central nervous system; GI, gastrointestinal.
DRUG-NUTRIENT INTERACTIONS
· Food can enhance or impede medication effects.
· Medication can influence food and nutrient intake, absorption, metabolism, and excretion.
· It is beyond the scope of this chapter to list all possible interactions; however, some common interactions may be found in Table 22-6.
TABLE 22-6 Important Food/Nutrient and Medication Interactions
DIETARY SUPPLEMENTS
· Products (other than tobacco) intended to supplement the diet that contain one or more of the following ingredients: a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance used to supplement a diet by increasing the total daily intake; or a concentrate, metabolite, constituent, extract, or combination of these ingredients (Table 22-7).
· Americans spend billions of dollars annually on supplements.
· Supplements do not require FDA approval and therefore vary greatly in strength, potency, and purity. Some products may contain no active ingredient. Contamination with pesticides, drugs, or heavy metals may occur, and it is the burden of the FDA to show that a product is not safe.
· Supplements may interact with other dietary supplements or prescription medications.
· Nonspecific side effects such as gastrointestinal (GI) distress, headache, allergic reactions, and medication interactions have been described for all supplements. Long-term effects of supplementation are not known.
· Some common complementary and alternative medicine dietary supplements are listed in Table 22-8.
TABLE 22-7 Common Dietary Supplements
aNational Institutes of Health grade of evidence for benefit.
A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence against this use
E: Strong scientific evidence against this use
bThe most recent grade of evidence for glucosamine and chondroitin in osteoarthritis was assigned before publication of the GAIT trial. Clegg DO, Reda DJ, Klein MA, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795–808.
cNIH evidence grading unavailable at this time.
ADHD, attention deficit hyperactivity disorder; ADP, adenosine diphosphate; LDL, low-density lipoprotein.
TABLE 22-8 Popular Herbal and Botanical Dietary Supplements
MAOIs, monoamine oxidase inhibitors; SSRIs, serotonin reuptake inhibitors; TCAs, tricyclic antidepressants.
Overnutrition and Obesity
GENERAL PRINCIPLES
· Overnutrition is the excess of one or more nutrients; it occurs when nutrient intake exceeds nutrient expenditure. Although macronutrients may be consumed in excess, micronutrient intake may be inadequate.
· Excess of vitamins and minerals can occur due to dietary supplements, complementary/alternative treatments, and some fad diets.
· Overweight is defined by BMI >25 kg/m2 and obesity BMI >30 kg/m2.
· Greater than 60% of Americans are overweight, >30% are obese, and approximately 5% are morbidly obese, and these rates have doubled in the past 20 years.1
· Obesity is associated with many comorbidities, including diabetes mellitus, hypertension, hyperlipidemia, atherosclerosis, gout, cardiovascular disease, and sleep apnea.
DIAGNOSIS
Clinical Presentation
History
· Obtain a general medical history including a careful diet history, thorough family history, and evaluation for medical and psychiatric comorbidities.
· When obesity is present, the evaluating physician should consider factors that affect intake and ability to perform physical exercise, and remember that obese patients may have micronutrient deficiencies.
o What quantity and type of foods are being consumed?
o What type of lifestyle does the patient lead?
o Is there evidence for secondary causes of obesity including genetic syndromes, hypothyroidism, insulinoma, or Cushing syndrome?
Physical Examination
· Distribution of body fat can be evaluated via waist to hip ratio although this is not routinely done in many offices and has significant operator variability.
· Comorbid conditions include insulin resistance, male hypogonadism, polycystic ovarian syndrome, cardiovascular disease, obstructive sleep apnea, gallstone disease, osteoarthritis, as well as component of bones and teeth and reproductive cancers.
Diagnostic Testing
Laboratory assessment in the obese patient should aim to assess comorbidities and rule out secondary causes, if suspected. At minimum, laboratory assessment should include a fasting lipid panel and fasting blood glucose in addition to blood pressure monitoring.
TREATMENT
Lifestyle changes (diet and exercise) are the cornerstones of weight loss, though medications and bariatric surgery can be considered when diet and exercise fail in certain populations. Treatment decisions must take into account each patient’s readiness for change (motivation, stress levels, time availability) and barriers to change.
Medications
· Indications for medical therapy include:
o BMI >30 kg/m2 or BMI >27 kg/m2 with concomitant obesity-related risk factors or diseases
o Unable to achieve weight loss goal despite therapeutic lifestyle changes
o No contraindications to use
· Weight loss medications are meant to be used as an adjunct to and not as a substitute for therapeutic lifestyle changes.
· They should be discontinued if the patient has not responded within 1 to 2 months.
· The use of such a medication should be considered long term (if not lifelong) in patients who respond, as patients will regain weight quickly if the drug is stopped.
· Medications approved for short-term use (phentermine, diethylpropion, benzphetamine, phendimetrazine) are not typically used because of their limitations on duration of use and addictive properties and will not be discussed further here.
Orlistat
· Orlistat works by inhibiting pancreatic lipase and reduces the absorption of fat by 30% at recommended doses.
· Studies have shown that patients who take orlistat and make therapeutic lifestyle changes will lose about 4% more weight than patients making therapeutic lifestyle changes alone.4
· Contraindicated in patients with malabsorption syndromes.
· Side effects include diarrhea, bowel incontinence, flatulence, and oily spotting.
· Interferes with absorption of fat-soluble vitamins, and a multivitamin should be taken to prevent deficiency.
· Costs approximately $2,600 per year of treatment at recommended doses.
· A half-strength over-the-counter version of orlistat is available under the trade name Alli.
o It inhibits fat absorption by 25% as compared with 30% for full-strength orlistat.
o Side effects are the same as for full-strength orlistat and are still significant despite the reduced dose.
o Costs approximately $500 to $700 per year.
Lorcaserin
· Lorcaserin was approved by the FDA in June 2012.
· It selectively activates 5-HT2C receptors and thought to centrally act to increase satiety by acting on anorexigenic proopiomelanocortin neurons in the hypothalamus.
· Studies have shown that patients who take lorcaserin and make therapeutic lifestyle changes lose ≥5% of their body weight compared to patients making therapeutic lifestyle changes alone, and lorcaserin also helps manage the weight loss for up to 2 years.5–8
· Contraindicated in pregnant patients.
· Side effects include headache, upper respiratory infections, nasopharyngitis, dizziness, nausea, vomiting, and diarrhea.
Phentermine/topiramate
· This combination was approved by the FDA in July 2012.
· Phentermine is a sympathomimetic substance that is thought to suppress appetite by releasing norepinephrine in the hypothalamus, resulting in increased serum leptin levels.
· Topiramate is thought to suppress appetite by augmenting GABA channels.
· Studies have shown phentermine/topiramate to increase the number of patients able to achieve and maintain >5% and >10% weight loss over placebo.9–11
· It is contraindicated in patients who are pregnant and with hyperthyroidism, glaucoma, or patients or have been on monoamine oxidase inhibitors within the previous 14 days.
· Side effects include constipation, dizziness, paraesthesia, and dry mouth.
Surgical Management
· Bariatric surgery is used as an adjunct to and not as a substitute for therapeutic lifestyle changes.
· Indications:
o BMI >40 kg/m2 or BMI 35 to 40 kg/m2 with life-threatening cardiopulmonary disease, severe diabetes, or lifestyle impairment
o Failure to achieve weight loss with other treatment modalities
· Contraindications:
o History of medical noncompliance
o Psychiatric illness
o High risk of death during the procedure
· Requires involvement of a team of medical, surgical, psychiatric, and nutrition experts.
· Most common current techniques include laparoscopic adjustable gastric banding and Roux-en-Y gastric bypass; less common techniques include biliopancreatic diversion and biliopancreatic diversion with duodenal switch.
· Patients should be aware of multiple complications and risks associated with the procedure. Complication rates are lower at centers with more experience.
Lifestyle/Risk Modification
· Decreasing caloric intake
o Set small goals and start with one or two small changes that the patient agrees to.
o Recommend substitutions (e.g., baked potato instead of french fries).
o Encourage more low-calorie foods at meals and for snacks.
o Recommend eating regular meals.
o Do not deny patients their favorite foods, but stress the importance of portion control.
o Discuss triggers to eating.
o Consider referral to a nutritionist/dietician.
· Increasing physical activity
o Helps sustain weight loss.12
o Activity should be recorded in an activity diary.
o Encourage 30 to 60 minutes of moderate physical activity on most days of the week.
o Encourage activities that your patient enjoys.
o Incorporate exercise into daily activities (e.g., walking to do nearby errands, ride your bike to work, walk the dog, take the stairs instead of the elevator).
Undernutrition
GENERAL PRINCIPLES
· Undernutrition is a deficiency of one or more nutrients and occurs when nutrient availability fails to meet metabolic requirements. It may result from inadequate nutrient intake, malabsorption, increased metabolic demands, ineffective substrate use, or any combination of these.
· The overall incidence of undernutrition in the US is not well defined but in hospitalized patients may be as high as 40% on admission, with those most undernourished risking further weight loss during the hospital course.13
· Undernutrition results in loss of skeletal and cardiac muscle function, impairment of immune function, apathy, depression, and prolonged hospital stays. Death can occur when weight falls to two-thirds of ideal body weight.14
· Risk factors for undernutrition include advanced age, chronic medical illnesses, drug-nutrient interactions, low socioeconomic status, and social isolation.
DIAGNOSIS
Clinical Presentation
History
· Obtain a complete diet history.
o Ask open-ended questions and be nonjudgmental.
o Have the patient fill out an eating pattern questionnaire (e.g., Eating Pattern Questionnaire from the American Medical Association).15
o Have the patient fill out a food diary for 3 to 7 days (e.g., Food and Activity Diary from the American Medical Association, a Web-based diary developed by the United States Department of Agriculture [USDA] is also available).2
· Evaluate for medical and psychiatric illnesses as well as surgical procedures that may affect energy or nutrient intake, absorption, or expenditure.
· Look for medications that may interact with nutrient absorption or stimulate appetite and cause weight gain.
· Screen for family history of conditions such as obesity, diabetes, and hyperlipidemia.
· Evaluate the patient’s psychosocial environment and substance abuse (alcoholism) that may predispose to micronutrient deficiencies.
· Review of systems should include screening for changes in weight.
Physical Examination
· Vital signs: blood pressure, heart rate, temperature, height, weight, and a calculation of BMI.
· Physical examination in the malnourished patient should focus on general appearance, skin, hair, nails, mucous membranes, and the neurologic system.
· The evaluating physician should consider factors that affect nutrient intake, absorption, and metabolism (Table 22-9).
Diagnostic Criteria
· Unintentional weight loss of 10% of body weight in the past 3 months
· BMI <18.5 kg/m2
TABLE 22-9 Causes of Malnutrition
Diagnostic Testing
· Laboratory assessment in the malnourished patient may include individual micronutrient levels and evaluation of systemic disease if suspected (e.g., thyroid function, HIV status).
· Serum albumin level is not generally recommended, as a depressed level is not specific for malnutrition. It is often depressed in overhydration, acute illness, or chronic liver, renal, or cardiopulmonary disease.16
REFERENCES
1.Food and Nutrition Board. Institute of Medicine. Dietary Reference Intake Tables. Available at: http://fnic.nal.usda.gov/dietary-guidance/dietary-reference-intakes/dri-tables, last accessed 1/5/15.
2.ChooseMyPlate.gov. Volume 2013: United States Department of Agriculture, 2012.
3.Hausenloy DJ, Yellon DM. Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. Heart 2008;94:706–714.
4.Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 2003;(3):CD004094.
5.Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 2011;96:3067–3077.
6.Martin CK, Redman LM, Zhang J, et al. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab2011;96:837–845.
7.O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring)2012;20:1426–1436.
8.Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010;363:245–256.
9.Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 2012;20:330–342.
10.Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011;377:1341–1352.
11.Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012;95:297–308.
12.Pavlou KN, Krey S, Steffee WP. Exercise as an adjunct to weight loss and maintenance in moderately obese subjects. Am J Clin Nutr 1989;49:1115–1123.
13.McWhirter JP, Pennington CR. Incidence and recognition of malnutrition in hospital. BMJ 1994;308:945–948.
14.Kotler D, Wang J, Pierson R. Studies of body composition in patients with acquired immunodeficiency syndrome. The United Nations University Press: Food Nutr Bull 1989;11:55–60.
15.Eating Pattern Questionnaire: American Medical Association, 2003.
16.Winter TA, O’Keefe SJ, Callanan M, et al. The effect of severe undernutrition and subsequent refeeding on whole-body metabolism and protein synthesis in human subjects. J Parenter Enteral Nutr2005;29:221–228.