Adult Weight Loss Diet : Metabolic Effects and Outcomes

1. 550251 NCPXXX10.1177/0884533614550251Nutrition in Clinical PracticeMatarese et al research-article2014 Adult Weight Loss Diet : Metabolic Effects and Outcomes Adult Weight Loss Diet : Metabolic Effects and Outcomes Invited Review Nutrition in Clinical Practice Volume XX Number X Month 201X 1 –9 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0884533614550251 ncp.sagepub.com hosted at online.sagepub.com Adult Weight Loss Diets: Metabolic Effects and Outcomes Laura E. Matarese, PhD, RDN, LDN, CNSC, FADA, FASPEN, FAND1,2; and Walter J. Pories, MD, FACS, FASMBS, FACC, FACG3 Preamble Abstract The global prevalence of overweight and obesity as a public health concern is well established and reflects the overall lack of success in our ability to achieve and maintain a healthy body weight. Being overweight and obese is associated with numerous comorbidities and is a risk factor for several of the leading causes of death, including cardiovascular disease, diabetes mellitus, and many types of cancer. The foundation of treatment has been diet and exercise. There are >1,000 published weight loss diets, with more appearing in the lay literature and the media on a regular basis. The sheer number of existing diet regimens would suggest that no one diet has been universally successful at inducing and maintaining weight loss. Many of these dietary programs are based on sound scientific evidence and follow contemporary principles of weight loss. Others simply eliminate 1 or more of the essential food groups or recommend consumption of 1 type of food at the expense of other foods with little to no supporting evidence. The focus of this review is on weight loss diets, specifically those with the most supporting scientific evidence and those that are most likely to succeed in achievement and maintenance of desirable body weight. The effects of weight loss diets on energy expenditure, body weight, body composition, and metabolic parameters will be evaluated. Ultimately, the best diet is the one the patient will follow and incorporate into his or her daily life for lifelong maintenance of a healthy body weight. (Nutr Clin Pract.XXXX;xx:xx-xx) Keywords Keywords body mass index; caloric restriction; weight loss; weight reduction programs; carbohydrate-restricted diet; fat-restricted diet; obesity; weight loss; glycemic index; Mediterranean diet Weight Loss Diets Weight Loss Diets The growing prevalence of overweight and obese individuals globally has risen to alarming rates. Currently, more than two- thirds of the adult population in the United States is either overweight or obese. The rest of the world is not far behind. These statistics alone are evidence of the overall failure of our ability to achieve and maintain a healthy body weight. Overweight and obesity are risk factors for several of the lead- ing causes of preventable death, including cardiovascular dis- ease, diabetes mellitus, and many types of cancer. Yet diet and physical activity are modifiable behaviors that can reduce the incidence of preventable diseases. Obesity is a serious and complex disease resulting from the interactions between predisposing genetic and metabolic fac- tors, cultural influences, a changing food supply, and a rapidly changing modern sedentary environment. Treatments for obe- sity include lifestyle modification such as diet, physical activity, and behavior modification as well as pharmacotherapy and sur- gery. Each of these interventions is important and carries spe- cific indications based on body mass index (BMI; Figure 1),1 even though BMI is a formula (BMI = kg/m2) that fails to account for gender, race, fitness, or age.2 However, in short, the foundation of effective obesity treatment centers on assisting the patient to make healthier dietary and physical activity choices that will lead to weight loss and a reversal of comor- bidities. The focus of this review is on weight loss diets and their effects on energy expenditure, body weight, body compo- sition, and metabolic parameters. Diet is food that is customarily consumed. The term diet is often used to refer to a weight-reduction diet. An estimated 1,000 weight loss diets have been developed, with more appearing in the lay literature and the media on a regular basis. The fact that there are so many diet plans available suggests that, to date, no one diet plan has been universally successful at inducing and maintaining weight loss. Some of these dietary intervention programs are based on sound scientific evidence (Table 1). Others simply eliminate one or more of the essential food groups or recommend consumption of one type of food at From 1Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, North Carolina; 2Department of Nutrition Science, East Carolina University, Greenville, North Carolina; and 3Department of Surgery, Brody School of Medicine, East Carolina University, Greenville, North Carolina. Financial disclosure: None declared. Corresponding Author: Laura E. Matarese, PhD, RDN, LDN, CNSC, FADA, FASPEN, FAND, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Brody School of Medicine and Department of Nutrition Science, East Carolina University, 600 Moye Blvd, Vidant MA 338, Greenville, NC 27834, USA. Email: mataresel@ecu.edu Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

2. What causes unplanned weight loss in older adults? What causes unplanned weight loss in older adults? Below are some common reasons why you may be losing weight without intending to: Eating too little food Eating too little food Not having enough money to buy food Not being able to go grocery shopping or cook or feed yourself Feeling depressed, sad, isolated and eating alone most of the time Having swallowing problems, mouth or tooth problems Not being able to smell, taste, chew or digest food properly Having an illness or a medical condition like cancer, heart conditions and digestive conditions such as ulcers or gall bladder disease Taking medications that may cause nausea and vomiting, difficulty swallowing, taste loss and poor appetite Drinking 3 or more alcoholic beverages every day When should I be concerned about my weight loss? When should I be concerned about my weight loss? Unplanned weight loss can lead to serious health effects. Speak to your doctor: If you have lost 4% to 5% or more of your body weight in the past 12 months without trying to or If you have lost 10% or more in a 5 to 10 year period or longer without trying to What can unplanned weight loss lead to? Unplanned weight loss may: Limit your ability to do day-to-day tasks Make a medical condition worse Increase your risk for muscle loss, infection, illness, depression and death How can I avoid weight loss? Making small changes to your eating habits throughout the day can help you avoid the health effects of unplanned weight loss. Read on for helpful nutrition tips. How can I avoid weight loss? Eat enough food Many older adults don’t eat enough food. This can increase the risk of weight loss and vitamin and mineral deficiencies. Try the following: Eat enough food Eat smaller meals more often. Choose high calorie and high protein foods at every meal and snack. Include full fat foods like cheese with 20% or more M.F. (milk fat) and 3% M.F. yogurt. Eat smaller meals more often. Eat foods with the right texture Dentures that don’t fit or missing teeth can make it hard to eat foods that you usually enjoy. Changing the way food is made or choosing different foods may help. Grind your food with a food processor. Cook your food longer to soften foods such as meat, vegetables and grains. Eat soft foods such as yogurt, meat loaf, avocado and eggs. Click on Eating Soft Foods for menu planning ideas. Eat foods with the right texture

3. 2 Nutrition in Clinical Practice XX(X) A Guide to Selecting Treatment BMI Category Treatment 25-26.9 27-29.9 30-34.9 35-39.9 ≥40 Appropriate NHLBI Guidelines Diet, physical activity, and behavior + + + + Not With co- morbidities + + + Pharmacotherapy appropriate Not Not With co- morbidities + Surgery appropriate appropriate Figure 1. Treatments for obesity. Adapted from the National Institute of Health, National Heart, Lung and Blood Institute. NIH Pub No. 00-4084, October 2000 (http://www.nhlbi.nih.gov/files/docs/guidelines/prctgd_c.pdf). the expense of other foods with little to no supporting evi- dence. These are commonly referred to as fad diets. Beyond the concept of thermodynamics, the biochemical, physiological, psychological, emotional, economic, and social factors surrounding mechanisms of weight loss are multifac- eted, interrelated, and dynamic (Figure 2). For example, physi- cal activity will influence the metabolic rate, which in turn affects insulin sensitivity and insulin resistance. Our food sup- ply has become more refined. This in turn affects satiety value due to the high concentration of refined sugar and low concen- tration of fiber. Levels of hormones such as ghrelin and leptin affect appetite and satiety level. When there are economic con- straints, people will purchase lost-cost foods, which tend to be low in nutrients but high in fat and refined carbohydrates. As we age, there is a reduction in lean body mass, metabolic rate, energy expenditure, and physical activity, all of which will result in increased weight gain if one continues to consume the same level of calories throughout the life span. This, along with many other factors, affects the gut microbiota, which in turn influences the storage and release of energy. This is part of the reason why effecting a significant and sustained weight loss has been so difficult. Obesity is a very complex disorder with multiple factors that are interrelated and dynamic. Factors Affecting Weight Loss Factors Affecting Weight Loss There are 4 laws of thermodynamics that define fundamental physical quantities (temperature, energy, and entropy) and that characterize thermodynamic systems. In their simplest terms, the laws of thermodynamics dictate the specifics for the move- ment of heat and work. As applied to maintenance of body weight, it is presumed that when energy consumption is equiv- alent to expenditure, weight is maintained; when energy con- sumption is greater than expenditure, storage of excess calories occurs; and when energy consumption is less than expenditure, there is mobilization of stored energy. But with regard to induc- tion of weight loss, is the equation really that simple? The sec- ond law of thermodynamics states that the entropy (a measure of the energy that is not available for work during the thermo- dynamic process) of the universe increases during any sponta- neous process. This is the law of dissipation, which pertains to chemical reactions. For any reaction that is irreversible, there is a loss or dissipation of energy in that reaction. In other words, metabolic processes are inefficient. Thus, it is impossi- ble for a system to turn a given amount of energy into an equiv- alent amount of work. It is this second law that shows that a “calorie” is not always a “calorie.” Energy is derived from chemical reactions in the body from the food we eat, which end up dissipating energy. Calories are not converted to energy on a one-to-one basis because of the loss of energy to the universe described by the second law. There is a larger loss of energy when one has to convert protein to sugar instead of merely oxi- dizing carbohydrate. Reduced thermodynamic efficiency will result in increased weight loss.3 Calories and Satiety Value Calories and Satiety Value Do the type and quality of macronutrients influence satiety value? Are 200 calories from celery the same as 200 calories from chocolate? It takes 1425 g of celery to supply 200 calories but only 36 g of chocolate to do the same. The difference is in the fat, water, and fiber content. These foods also have differ- ences in satiety value, which appears to be related to the volume and macronutrient content. Macronutrients with the same caloric content exert different effects on satiation and satiety independent of their caloric value.4,5 Under normal metabolic Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

4. 3 Matarese et al Table 1. Comparison of Weight Loss Diets.a Diet Advantages Disadvantages Exercise Behavioral Modification • • Rapid initial weight loss • • Emphasis on healthy fats • • High satiety value • • Slow introduction of complex carbohydrates • • Halitosis from ketone production • • Must adjust insulin for reduction in body weight and carbohydrate intake • • Low fiber; may cause constipation • • Complex; must adhere to caloric ratio of carbohydrate, protein, and fats (40-30-30) • • Must weigh food • • Suggests walking as the best way to begin • • Discussion of aerobic vs anaerobic activities • • Assessment of maximum heart rate, best frequency, duration, intensity of workouts • • Walking for the calorie-burning and hormonal benefits, but for fat burning, you have to eat a Zone snack both 30 min before and 30 min after exercising • • No specific fitness plan, but recommends gradually building up to 30–60 min of walking or other moderate activity each day. • • Encourages lifelong changes for sustained weight loss Very low carbohydrate Atkins Low fiber; may cause constipation • • Rapid initial weight loss • • Emphasis on healthy fats • • High satiety value • • No; diet is designed to get client into “the Zone,” requiring a regimented, one-size- fits-all method of eating Low glycemic Zone • • Results in significant weight loss • • Extremely limited and difficult to follow • • Poor long-term compliance • • Low fat often resulted in consumption of increased calories • • Very low fat, which may be difficult to follow long term • • Stress management • • The choice-based program emphasizes becoming aware of what is eaten Low fat Ornish • • Results in significant weight loss • • Flexible food choices • • Includes exercise • • Intensified structured approach to health behavior modification with a focus on healthy eating, exercise, coping patterns, and sustained weight loss • • Healthful behavior strategies • • Web site offers articles to help avoid common mental pitfalls that can sabotage weight loss LEARN • • Nutritionally balanced • • Can potentially abuse point system • • Some; workout ideas, demonstrations online • • Program includes general guidelines from U.S. Centers for Disease Control and Prevention and the American College of Sports Medicine • • General; 30 min of exercise per day in small increments whether you are dieting or not • • 45–60 min of aerobic activity each day for weight loss • • Includes a 3-day exercise plan Weight Watchers • • Nutritionally balanced • • Not restrictive • • Definition of Mediterranean diet varies • • Indirectly; suggestions to use smaller plates and eat slowly Mediterranean diet aAdapted with permission: Matarese LE, Kandil HM. Weight loss diets: weighing the evidence. In: Mullin GE, Cheskin LJ and Matarese LE, eds., Integrative Weight Management: A Guide for Clinicians. New York, NY: Humana Press; 2014. Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

5. 4 Nutrition in Clinical Practice XX(X) Body composition (muscle vs. fat) Behaviors Changing food supply Age Diet composition Satiety Fac F F a a ac a F Factors Influencing Weight Loss W W W W W ht gh W W W W Weight W W igh ht h t t t c ctors I o o to o tors I t rs s s In uenc nc c c c g g ng ing s cin in ng cin n g Economics Lo Loss Religious & cultural practices Medications Interrelated and Dynamic lat n rr t n Inter ed and d Dy nd d d y na a am na n mic na am mic am m Metabolic rate: •Physical activity •Thermic effect of foodstuffs •REE Genetics Gut microbiota Insulin sensitivity Insulin resistance Hormones: Ghrelin Hormones: Ghrelin Leptin Leptin Figure 2. Factors influencing weight loss. circumstances, protein has the greatest effect on satiety.6-9 Interestingly, high-fat foods have a lower satiety score compared with carbohydrates, which are rich in fiber and water. Rolls and colleagues10 conducted a trial to determine the effects of energy density and portion size on sustained decreases in energy intake. In a crossover trial, 24 women were provided all meals for 2 consecutive days for 4 weeks and were allowed to eat ad libitum. The subjects were served the same menus but with variations in the portion size and energy density. Reductions in energy density and portion size independently influence energy intake, and there were no significant differences in ratings of hunger or full- ness. The reduction in intake was greatest with the combined reduction of lower energy density and smaller portion. In coun- seling clients, it should be noted that small changes in portion size and energy density could result in reduced intake. results in changes in energy expenditure. In a randomized parallel-design study, overweight or obese young adults (n = 39, 18–40 years) received an energy-restricted diet with a variation in the carbohydrate or fat content, either low-gly- cemic load or low-fat diet.11 Both groups were allowed to achieve a 10% weight loss and then had their resting energy expenditure (REE) measured. REE decreased less with the low-glycemic load diet vs low-fat diet (96 ± 24 vs 176 ± 27 kcal/d), thus making it easier to lose weight on the low-gly- cemic diet. The difference amounted to about 80 kcal/d. Over the course of a year, this would amount to about 30,000 kcal and an average weight loss of about 8 pounds. In addi- tion, participants receiving the low–glycemic load diet reported less hunger than those receiving the low-fat diet (P = .04), had greater improvement in insulin resistance (P = .01), serum triglyceride levels (P = .01), C-reactive protein levels (P = .03), and blood pressure (P = .07). To evaluate the effects of macronutrient composition on energy expenditure during weight loss, Ebbeling and col- leagues12 conducted a controlled 3-way crossover study of overweight and obese young adults (n = 21). The study included Energy Expenditure and Macronutrient Composition Composition There are data to suggest that altering the macronutrient composition of the diet provides a metabolic advantage and Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

6. 5 Matarese et al parameters? Historically, a healthy diet was defined as ≥55% carbohydrate, ≤30% fat, and approximately 15% protein.18 Altering the macronutrient content of the diet involves more than changing the percentage contribution from carbohydrate, fat, and protein. A carbohydrate is not simply a uniform organic compound. Changes in the carbohydrate content of the diet may be based on the glycemic index or glycemic load, the fiber content of the specific carbohydrate or complex carbohydrates vs refined. Yet these are all carbohydrates, which potentially can be altered in the diet and may have different metabolic effects. These carbohydrates will vary in their influences on blood sugar, nutrient density, and hormone levels, all of which affect tissue metabolism. The same is true for fat. A fat is sim- ply not one nutrient but rather comprises a collection of mono- unsaturated, polyunsaturated, saturated fats, and trans fats. They may include ω-3, ω-6, or ω-9 fatty acids, all of which have significant effects on inflammation, a major component of obesity. Protein sources may be derived from plant, marine, or animal sources. It should also be noted that these macronu- trients cannot be considered in isolation. As the percentage of 1 of these macronutrients in the diet is reduced, the percentage of the other 2 macronutrients will increase. One of the most popular and well-studied alterations in macronutrient content is carbohydrate. The reason for a carbo- hydrate restriction is to reduce serum insulin levels and force a change in substrate metabolism. Low-carbohydrate diets reduce the dietary contribution to serum glucose, which lowers insulin levels. Because insulin is an anabolic hormone and a potent stimulator of lipogenesis and inhibitor of lipolysis, low- ering insulin levels allows utilization of stored body fat for energy. Dietary carbohydrate restriction also leads to appetite suppression and reduced caloric intake. It is also possible that inefficient protein and fat oxidation leads to extra energy loss.19 This relates back to the second law of thermodynamics. In many cases, lipolysis is maintained despite excess calories because glycerol from fat is needed as a gluconeogenic precur- sor.20 The exact carbohydrate level required to produce this metabolic shift is thought to be between 20 and 50 g per day in the initial phases of the diet in comparison with the carbohy- drate content of the typical Western diet, which often exceeds 300 g per day. There have been numerous studies that have evaluated the effects of low-carbohydrate vs low-fat diets in the management of obesity and its comorbidities. In a systematic review of ran- domized controlled trials of low-carbohydrate, high-protein diets vs low-fat diets, the low-carbohydrate, high-protein diets were more effective at 6 months and are as effective, if not more, as the low-fat diets in reducing weight and cardiovascu- lar risk parameters (HDL, triglycerides, systolic blood pres- sure) risk up to 1 year.21 Hu and colleagues22 performed a meta-analysis of randomized controlled clinical trials of low- carbohydrate (≤45%) vs low-fat (≤30%) diets to determine if differences in the macronutrient content resulted in differences in weight loss, body composition, and risk factors for diabetes a run-in phase in which calories were restricted to achieve a 10% to 15% weight loss. The diet was composed of 45% carbo- hydrate, 30% fat, and 25% protein. In random order, subjects were assigned isocaloric diets each for 4 weeks, either a low- fat, high–glycemic load (60% carbohydrate, 20% fat, 20% pro- tein); low–glycemic index (40% carbohydrate, 40% fat, 20% protein); or a very-low-carbohydrate, low–glycemic load (10% carbohydrate, 60% fat, 30% protein) diet. Energy expenditure was then measured. The reduction in REE and total energy expenditure (TEE) was the highest in the low-fat group, which would make weight loss more difficult. The reduction in energy expenditure was least with the very-low- carbohydrate high- protein diet. Thus, it appears that isocaloric is not necessarily isometabolic and that there is a metabolic advantage in altering the macronutrient composition to include higher levels of protein. There are some limitations and ambiguities associated with the evaluation of energy expenditure in weight loss. Measurement of energy expenditure is considered to be the most reliable method of determining energy requirements. The accuracy of properly calibrated indirect calorimeters is gener- ally high, with errors of <4%. However, there can be some variation in measurement due to methodology, time, and dura- tion of testing. The exact mechanism and physiological basis for the differences in energy expenditure remains unclear and probably results from a number of factors. The thermic effect of food (the increase in energy expenditure arising from diges- tive and metabolic processes) may be a factor. Protein has a high thermic effect of food.13 There is also a high energy cost associated with the hydrolysis of a single peptide bond, requir- ing 4 ATPs per bond formed. Thus, the energy costs of protein turnover could account for this metabolic advantage in high- protein diets.14 Other possible explanations for the observed differences in energy expenditure may involve changes in hor- mones affecting metabolic pathways and lean muscle effi- ciency.15-17 Although the exact mechanisms are unclear, it is apparent that altering the macronutrient component of the diet does result in metabolic changes. Macronutrient Modification and Resulting Macronutrient Modification and Resulting Metabolic Effects Metabolic Effects Metabolic Syndrome Metabolic Syndrome The major concerns with obesity are the related comorbid con- ditions as seen in metabolic syndrome (MetS) and type 2 dia- betes mellitus. MetS is a disorder of energy utilization and storage and is generally categorized by central obesity, hyper- tension, elevated fasting plasma glucose and insulin levels, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol levels. MetS increases the risk of developing car- diovascular disease, particularly heart failure, and diabetes. The question arises, does modification in macronutrient con- tent affect actual weight loss, body composition, and metabolic Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

7. 6 Nutrition in Clinical Practice XX(X) and cardiovascular disease. Twenty-three trials with a total of 2,788 participants were included in the analysis. Both the low- carbohydrate and low-fat diets resulted in a decrease in body weight, waist circumference, blood pressure, total to HDL cho- lesterol ratios, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, blood glucose, and serum insulin levels. Both diets resulted in an increase in HDL cholesterol. However, participants on low-carbohydrate diets had greater increases in HDL cholesterol and greater decreases in triglyc- erides but experienced less reduction in total and LDL choles- terol compared with persons on low-fat diets. This suggests that the low-carbohydrate diets are as effective in reducing weight and improving specific metabolic risk factors and may be more efficacious in certain individuals. Many of the comparative trials evaluating the effective- ness and safety of weight loss diets have been limited by short follow-up times and high dropout rates. In a 2-year interventional trial, Shai et al23 randomly assigned 322 mod- erately obese subjects to 1 of 3 diets: low fat (<30%), restricted calorie; Mediterranean (<35% fat), restricted calo- rie; or low carbohydrate (<20 g/d), non–restricted calorie. The rate of adherence to the assigned study diet was 95.4% at 1 year and 84.6% at 2 years. The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean diet group, and 4.7 kg for the low-carbohydrate group (P < .001). In addition, the relative reduction in the ratio of total cholesterol to HDL cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P = .01). Among the 36 sub- jects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low- fat diet (P < .001). Brehm and colleagues24 conducted a randomized trial comparing a very-low-carbohydrate diet and a calorie- restricted low-fat diet on body weight and cardiovascular risk factors in healthy women. Subjects were randomized to a calorie-restricted low-fat diet (n = 27) or an ad libitum low- carbohydrate ketogenic diet (n = 26). Weight lost and reduc- tion of body fat as measured by dual x-ray absorptiometry was significantly greater in the very-low-carbohydrate keto- genic group compared with the low-fat group at 3 and 6 months (P < .001). Mean levels of blood pressure, lipids, fast- ing glucose, and insulin were within reference ranges in both groups at baseline and improved over the course of the study for both groups. Eighty-five percent of the subjects on the low-carbohydrate diet completed the study, compared with 74% on the low-fat diet. The authors concluded that a low- carbohydrate diet is more effective than a low-fat diet for short-term weight loss and, over 6 months, is not associated with deleterious effects on cardiovascular risk factors in healthy women. This is one of the few studies that evaluated the composition of the weight loss. There have been a few other small studies that have assessed body composition in response to a low-calorie carbohydrate-restricted diet.25-28 In each case, a carbohydrate-restricted diet low in energy resulted in greater loss of fat mass and preservation of lean body mass. Considering the increased risk of cardiovascular disease associated with MetS, Dansinger and colleagues29 evaluated the effectiveness and adherence rates of 4 popular weight loss diets on overweight or obese adults with known hypertension, dyslipidemia, or fasting hyperglycemia. Subjects were ran- domly assigned to receive Atkins, Zone, Weight Watchers, or the Ornish diet over the course of 1 year under normal free- living conditions.29 All of the diets resulted in modest statisti- cally significant weight loss at 1 year, with no statistically significant differences between diets. Overall dietary adher- ence rates were low, although increased adherence was associ- ated with greater weight loss and cardiac risk factor reductions for each diet group. The discontinuation rates among the diets were 50% for Ornish, 48% for Atkins, and 35% for both Zone and Weight Watchers. Each of the diets achieved modest sta- tistically significant improvements in several cardiac risk fac- tors, although these reductions were associated with weight loss regardless of diet type. A similar study was conducted by Gardner and colleagues.30 The A to Z study was designed to test the 12-month effectiveness of 4 different weight loss diets among 311 overweight or obese, nondiabetic, premenopausal women. The study had a public health focus in that the researchers were trying to mimic real-life conditions in which someone would simply purchase a weight loss diet book. Study participants were randomly assigned to follow the Atkins (15% carbohydrate), Zone (40% carbohydrate), LEARN (60% carbohydrate), or Ornish (70% carbohydrate) diets. They were asked to read the respective weight loss book and received weekly instruction from a registered dietitian for 2 months to ensure comprehension of the assigned diet plan. There were e-mail and phone reminders as well as incentives for study completion. After 12 months, the Atkins group had a mean weight loss of 4.7 kg while the other 3 groups had mean losses of 1.6–2.6 kg. Women in the Atkins group also had more favorable outcomes for metabolic parameters at 1 year than women assigned to the Zone, Ornish, or LEARN diets. Whether the improved risk profile was due to the absolute weight loss or diet composition is not clear, as the study was not designed to answer this question. Adherence to the vari- ous dietary regimens was not optimal and reflected the real- world challenges associated with reading and following guidelines in popular diet books. However, the results of this study demonstrate comparable or greater weight loss with the Atkins diet in the absence of adverse metabolic effects. These results were confirmed in a recent randomized, parallel-group trial which demonstrated that the low carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet.31 A recent meta-analysis of several weight-loss diets confirmed that the largest weight loss occurs with the low-carbohydrate diet both at 6 and 12 months. However, any diet intervention is likely to result in weight loss.32 Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

8. 7 Matarese et al Besides metabolic effects, Gardner and colleagues33 evalu- ated the nutrient content of each diet. Of the 4 diet groups, the Zone diet provided the most optimal micronutrient levels dur- ing energy restriction. This highlights the importance of includ- ing vitamin supplementation in those weight loss diets that may not supply 100% of the dietary reference intakes. In a sec- ondary analysis, the level of dietary adherence and long-term compliance was evaluated and revealed that regardless of the assigned weight loss diet, 12-month weight change was greater in the most adherent compared with the least adherent sub- jects.33 These results s suggest that strategies to increase com- pliance may be be as important as the specific macronutrient composition of the diet itself in supporting long-term success. Certainly, compliance with any diet is important for optimal results. However, other factors such as the degree of insulin resistance or sensitivity may determine the effectiveness of dietary macronutrient composition on weight loss. Obese non- diabetic women who were insulin sensitive (n = 12) or insulin resistant (n = 9) participated in a 4-month feeding study.34 They were provided with 2 diets: a high-carbohydrate low-fat (60% carbohydrate, 20% fat) or a low-carbohydrate high-fat (40% carbohydrate and 40% fat) diet. All of the food was provided to the participants. The high-carbohydrate low-fat diet was more effective in inducing weight loss for insulin-sensitive women (P < .01), while the low-carbohydrate high-fat diet was more effective for insulin-resistant women (P < .05). The differences were not explained by changes in intake, activity, or resting metabolic rate. A similar trial was conducted to evaluate the effects of a low–glycemic load vs low-fat diet in nondiabetic obese young adults (aged 18–35 years; n = 73).35 Subjects were randomized to a low–glycemic load diet (40% carbohydrate and 35% fat) or low-fat diet (55% carbohydrate and 20% fat) for a 6-month intensive intervention period with a 12-month follow-up period. Serum insulin concentration was measured at 30 min after a 75-g dose of oral glucose determined at baseline as a measure of insulin secretion. The low–glycemic load diet was more effective in inducing weight loss in those individuals who were insulin resistant. Thus, the choice of weight loss diet may in part be determined by whether the individual is insulin resis- tant or insulin sensitive. One of the issues in conducting these trials is the definition of insulin resistance vs insulin sensitiv- ity. This may be defined by reduced insulin secretion during an intravenous glucose tolerance test.36 dietary interventions in individuals with type 2 diabetes over the short and long term. The effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes was evaluated by Boden and colleagues.37 Ten obese patients with type 2 diabetes were provided their usual diets for 7 days followed by a low-carbo- hydrate diet for 14 days. The study was conducted in a con- trolled inpatient setting. While on the low-carbohydrate diet, there was a spontaneous reduction in energy intake with weight loss that was accounted for by reduced caloric intake. In addi- tion, improved 24-hour blood glucose, insulin sensitivity, and HbA1c levels, as well as decreased plasma triglyceride and cholesterol levels, were observed. The low-carbohydrate diet reduced the postprandial glycemic/insulin response in these patients. Yancy and colleagues38 conducted a pilot study to evaluate the efficacy, safety, and metabolic effects of a low-carbohy- drate, ketogenic diet (LCKD) in overweight patients with type 2 diabetes over the course of 16 weeks. Seven subjects aged 35–75 years with a BMI of >25 kg/m2 who were being treated with oral hypoglycemic agents and/or insulin, or who had an HbA1c >6.0% without medications, were instructed on LCKD with an initial goal of <20 g carbohydrate per day. The LCKD improved glycemic control to the extent that the diabetes medi- cations were discontinued or reduced in most participants. Mean body weight decreased by 6.6%, and fasting serum tri- glycerides decreased by 42%. The short-term effects of severe dietary carbohydrate restric- tion in patients with poorly controlled type 2 diabetes were eval- uated by Daly and colleagues.39 Patients with type 2 diabetes (n = 120, HbA1c = 8%–12%, BMI >30 kg/m2) were randomized to receive a standard diet instruction consisting of reducing fat intake and portion size or low-carbohydrate diet instruction con- sisting of <70 g carbohydrate per day. Each group received 3 monthly group sessions. Weight loss was greater in the low-car- bohydrate group (–3.55 ± 0.63 kg vs –0.92 ± 0.40 kg, P = .001). There was a greater improvement in the ratio of cholesterol to HDL (–0.48 ± 0.11 vs –0.10 ± 0.10, P = .01) in the low-carbohy- drate group compared with the low-fat group. In this study, car- bohydrate restriction was capable of inducing short-term weight loss compared with standard approaches. Many of these studies were short term and evaluated a low- carbohydrate diet against a standard diet. But are the beneficial effects due to the type of macronutrient or the amount? Westman and colleagues40 tested the hypothesis that a low- carbohydrate diet would lead to greater improvement in glyce- mic control over a 3-month period in obese patients and type 2 diabetes compared with a low–glycemic index diet. Eighty- four individuals with obesity and type 2 diabetes were random- ized to either an LCKD containing <20 g of carbohydrate or a low-glycemic, reduced-calorie diet prescribed at 500 kcal/d deficit from weight maintenance. Both groups received group meetings, nutrition supplements, and exercise recommenda- tions. Forty-nine participants completed the study. Both Ten obese patients with type 2 diabetes were Type 2 Diabetes Type 2 Diabetes Individuals with type 2 diabetes will have improved metabolic parameters with weight loss. Insulin resistance is the primary feature underlying type 2 diabetes. Dietary carbohydrate is the major determinant of postprandial glucose levels. Thus, if the carbohydrate content of the diet is altered, will there be a posi- tive effect on weight loss and other metabolic parameters? A number of well-controlled trials have evaluated the effects of Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014

9. 8 Nutrition in Clinical Practice XX(X) interventions led to improvements in HbA1c, fasting glucose, fasting insulin, and weight loss. However, the LCKD resulted in greater improvements in HbA1c (–1.5% vs –0.5%, P = .03), body weight (–11.1 kg vs –6.9 kg, P = .008), and high-density lipoprotein cholesterol (+5.6 mg/dL vs 0 mg/dL, P < .001) compared with the low-glycemic diet. Medications to control diabetes were reduced or eliminated in 95.2% of the LCKD group compared with 62% of the low-glycemic index diet group (P < .01). One of the largest studies of dietary intervention in type 2 diabetes was conducted by Hussain et al.41 Three hundred sixty-three overweight and obese participants (102 had type 2 diabetes) were recruited for a 24-week diet intervention trial. The participants were allowed to choose a low-calorie diet (LCD) or an LCKD. Body weight, BMI, changes in waist cir- cumference, blood glucose level, changes in HbA1c, total cho- lesterol, LDL cholesterol, HDL cholesterol, triglycerides, uric acid, urea, and creatinine levels were determined before and at 4, 8, 12, 16, 20, and 24 weeks after the administration of the LCD or LCKD. The initial dose of some antidiabetic medica- tions was decreased to half, and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. Both diets had beneficial effects on all of the parameters examined. However, these changes were more sig- nificant in subjects who were on the LCKD as compared with those on the LCD. Most of the trials evaluating dietary intervention looked at short-term metabolic outcomes such as actual weight loss, changes in HbA1c, lipid profiles, and changes in medication dosages. The Look AHEAD trial evaluated whether modest weight loss from lifestyle intervention would reduce the rate of heart attacks and strokes to a lower level than that seen among similar participants assigned to the diabetes education and sup- port group.42 All participants received routine medical care from their own healthcare provider. This landmark study enrolled >5,000 overweight and obese patients with diabetes, with a planned follow-up period of up to 13 years. However, the trial was stopped after 11 years after the trial’s Data and Safety Monitoring Board reviewed the data and concluded that there was no difference in the rates of heart attacks and strokes. It is noteworthy that the overall rates of heart attacks and strokes among both groups of patients were much lower than had been anticipated. protein including marine (ω-3), plant (with fiber), and lean ani- mal (low in saturated fat) sources. Choosing the Best Diet Unfortunately, there is no one diet that is universally accepted to induce weight loss in all circumstances. Choosing the best diet plan for an individual is not easy. There are numerous factors to consider, such as the degree of obesity and associated comor- bidities. Whether to select a low-carbohydrate or a low-fat diet may be based on whether the patient is insulin resistant or insu- lin sensitive. Obesity has been linked to many cancers, and diets high in fat and red meat have been linked to cancer. The question comes up as to whether or not these individuals should be placed on low-carbohydrate, high-protein diets since they tend to be high in fat and, often, red meat. For some of these patients, adop- tion of the Mediterranean diet may be more appropriate. The Mediterranean diet has been shown to reduce body weight and is rich in foods that are high in antioxidants. Medications should be carefully evaluated. Oftentimes, patients may be on medications affecting appetite. Food intake and physical activity should be considered. In addition, the type of dietary approach the patient might adhere to and the patient’s readiness to change are major factors. Finally, the degree of patient literacy will affect the choice of diet. There are some patients who simply cannot read or are unable to do simple math. For many of these patients, the best advice is to have them eat half of what they normally eat. It may not be optimal, but it may be the best that can be achieved in a free-living situation. Summary Summary Achievement and maintenance of a healthy body weight is not easy. There are numerous factors that impact metabolism. A “calorie” is not always a “calorie.” Calories from foods that are less satiating can lead to overconsumption. Macronutrient dis- tribution can affect satiety and therefore intake and resultant weight loss. With regard to energy balance, “isocaloric” is not necessarily “isometabolic.” Low–glycemic index and low-car- bohydrate diets can beneficially affect REE and TEE. Individuals who are insulin resistant may have better weight loss and maintenance with a low-carbohydrate diet compared with a low-fat diet, but a high-carbohydrate, low-fat diet may be more effective for insulin-sensitive individuals. High-risk patients should be medically supervised and carefully moni- tored. Ultimately, the best diet is the one the patient will follow and incorporate into his or her daily life for lifelong mainte- nance of a healthy body weight. Caveats for Macronutrient Modification Caveats for Macronutrient Modification Merely modifying the percentages of carbohydrate, protein, and fat is an oversimplification. The patient must be instructed to include complex carbohydrates, which are high in fiber, have a low glycemic index, have high water content, and are less refined/simple. Healthy fats (mono- and polyunsaturated, ω-3 fatty acids) and less unhealthy fats (saturated, trans fats) should be included. Protein should be high-biological-value References 1. National Institutes of Health, National Heart, Lung and Blood Institute. NIH Pub No. 00-4084; October 2000. 2. Pories WJ, Dohm LG, Mansfield CJ. Beyond the BMI: the search for bet- ter guidelines for bariatric surgery. Obesity. 2010;18(5):865-871. Downloaded from ncp.sagepub.com at East Carolina University on October 8, 2014