Obesity: Is There Effective Treatment?

ABSTRACT: Screen patients regularly to evaluate their risk of obesity. The body mass index is a useful tool that can be recorded as the fifth vital sign during routine checkups. Any successful long-term weight-loss intervention must include dietary modification and caloric restriction. Compliance is more important than the type of diet. Physical activity helps patients lose weight and maintain weight loss. A minimum of 150 minutes over 3 to 7 days is recommended. Orlistat and sibutramine are reserved for obese patients and work best in conjunction with lifestyle changes. However, they cannot be taken for more than 2 years, and most patients regain their lost weight. Bariatric surgery is indicated for persons with the highest body mass index who do not respond to other interventions.
                               

Despite widespread efforts at weight control, Americans are getting heavier.1 Obesity, defined as a body mass index (BMI) of 30 kg/m2 or more, is quickly becoming one of the most important medical challenges in the United States.2

The incidence of obesity is skyrocketing, and no age group is spared.1,3 In adults, the obesity rate has nearly tripled, from 13% to 31%, over the past 40 years.2 A similar 3-fold increase has been observed in children aged 6 to 11 years. In persons aged 12 to 19 years, the incidence of obesity is more than 3 times higher than it was 20 years ago.4 The magnitude of the problem is even greater for young persons in minority groups; the incidence of obesity among these young persons has quadrupled, from 6.5% to 27.4%, over the past 12 years.5

This is worrisome, because evidence suggests that about 20% of obese 4-year-olds and 80% of obese adolescents remain obese into and throughout adulthood. Moreover, such complications of obesity as diabetes, obstructive sleep apnea, depression, hypertension, steatohepatitis, polycystic ovary syndrome, dyslipidemia, exercise intolerance, and musculoskeletal problems are developing earlier.6

The unprecedented obesity epidemic threatens to reverse the trend toward longer life expectancy that has been carefully cultivated over the past several generations of Americans. Compared with a normal-weight person, a 20 year-old with a BMI higher than 45 kg/m2 can expect to live 13 years less than normal-weight counterpartsif male, and 8 years less if female.7 If the current trend continues, obesity may curtail overall life expectancy by up to 5 years sometime during this century.8 This would make the next generation the first to exhibit a shortened life expectancy in the modern era.

In this article, we review the factors that contribute to obesity. We then describe effective approaches to weight control, including exercise, dietary modification, drug treatment, and bariatric surgery.

CAUSES OF OBESITY

A person's weight depends on the balance between calories consumed and calories expended. During the past 4 decades, energy-dense and refined foods have become more available. Consumption of sweetened beverages, fast food, and larger portion sizes contribute substantially to excessive calorie intake.

Americans are also becoming increasingly sedentary. Desk jobs are more prevalent than ever, and leisure pursuits often center around computers, videos and video games, and television. Physical education programs are disappearing from the curriculum at many schools. The safety and availability of parks, public playgrounds, and pedestrian walking and bicycle paths have decreased. Walking, running, and biking have given way to motorized travel, even for the shortest distances.4

Risk factors

Infants. Obesity risks start before birth. Maternal cigarette smoking, obesity, and gestational diabetes increase an infant's chances of maturing into an obese child or adult. Breast-feeding reduces this risk.9-11

Children. The principal contributor to childhood obesity is a sedentary lifestyle combined with a diet high in calories and junk food. Physical activity is difficult to measure accurately in young children, but specific sedentary activities are linked to obesity. For instance, watching 5 or more hours of television per day (compared with less than 1 hour) confers a relative risk of 2.53 to 2.63 for obesity in 8- to 16-year-olds.12 Children who watch a great deal of television consume more total calories and energy-dense foods than children who do not.13

Children are also drinking 2 to 3 times as many soft drinks now as they did in the 1960s.14 The effects of this consumption are cumulative: an adolescent who consumes just 1 additional soft drink per day increases his or her risk of obesity by 60% over 19 months.15

Teenagers. Adolescents have risk factors for obesity similar to those of children but face additional challenges. Increased freedom and spending money may lead to consumption of fewer meals at home and more in restaurants. The food served in restaurants and fast-food chains typically is more calorie-dense and is served in larger portions than food served at home. One meal consisting of a double cheeseburger, French fries, soft drink, and dessert could contain as many as 2200 kcal. A teenager would need to run a full marathon to burn off these calories (based on a calorie expenditure rate of 85 kcal/mile).6

Dietary content is also important. Home-cooked meals typically contain more fruit and fiber than restaurant food. One study showed that persons aged 18 to 30 years who had the highest fiber intake weighed, on average, 3.65 kg less and had fewer markers of the metabolic syndrome than persons who consumed the least fiber.16

Participation in physical activity progressively decreases during adolescence. In 2003, a survey showed that only 28% of high school students participated in daily physical education and only 24% engaged in moderate physical activity for 30 minutes on 5 or more days per week.6

Adolescents who begin smoking also increase their risk of obesity. Smokers tend to be sedentary and to eat an unhealthful diet (low-fiber, high-calorie foods), both of which foster weight gain.16

Adults. Improper diet is a key contributor to obesity in adults. Data show a direct link between consumption of fiber and whole grains, low BMI, and long-term (2 to 4 years) weight control. Conversely, consumption of refined grains increases the risk of obesity and insulin resistance.17 Intake of nuts and peanut butter is an important factor in weight control. One study showed that persons who ate 5 or more 1-oz servings of nuts per week had a somewhat lower risk of obesity and a 50% reduction in adverse cardiovascular events compared with those who consumed less than 1 serving per week.18

Sedentary behavior is clearly associated with adult obesity. Women increase their risk of obesity by 23% for each 2 h/d they spend watching television and by 5% for every 2 h/d they sit at work. Standing or walking around at home for 1 h/d reduces obesity risk by 9%, and 1 h/d of brisk walking reduces it by 24%.19

SCREENING

A simple obesity screening tool is the BMI, which correlates well with body fat and health risks.The BMI can be measured during regular office visits as a fifth vital sign (Box I).20,21 Obesity screening and prevention should be continued throughout a patient's lifetime.


I - Calculating BMI
The body mass index (BMI) is a simple tool for determining whether a person is underweight, normal weight, overweight, or obese. To calculate a person's BMI, determine his or her height and weight, and apply the following formula:

English formula:
BMI = [weight in lb/(height in inches) × (height in inches)] × 703

Metric formula:
BMI = [weight in kg/(height in cm) × (height in cm)] × 10,000

An instant BMI calculator is also available at: www.cdc.gov/nccdphp/dnpa/bmi/calc-bmi.htm.

BMI values for adults are as follows:

BMI, kg/m² Weight status

< 18.5 Underweight

18.5 - 24.9 Normal

25 - 29.9 Overweight

≥ 30  Obese


TREATMENT

Obesity is difficult to manage. Approximately 85% of dieters regain lost pounds within a year, and 95% of them cannot maintain a 5% weight loss for 5 years.22

Many studies of obesity interventions have serious shortcomings and limitations:

  • Most overrepresent upper-income white women.
  • Almost all studies involve volunteers, who are more motivated than average patients.
  • Dropout rates are usually high, and results are typically reported only for persons who complete treatment. This number is usually below the 80% of recruited participants recommended by many authorities (including the Centre for Evidence-Based Medicine) for results to be considered adequate.
  • In the few studies that have used intent-to-treat analysis, the last known weight was carried forward. Because most patients regain their weight, an intent-to-treat analysis may yield a falsely increased final weight loss for patients who are lost to follow-up.2
  • Most studies are conducted in an intensive research environment, which is difficult to reproduce in community practice.
  • There is little good scientific information about long-term weight loss. Most studies monitor short-term weight loss; some follow such short-term secondary outcomes as cholesterol level, diabetes status, and blood pressure. Although long-term weight loss has not been conclusively and directly proved to reduce mortality, it ameliorates many of the risk factors that contribute to mortality, such as elevated blood pressure and insulin levels and dyslipidemia.

These challenges do not mean that obese persons are beyond help. Several effective approaches to weight control are available. These include dietary modification, exercise, behavior modification, drug treatment and, when these measures are ineffective or insufficient, bariatric surgery. Specific interventions that have been shown in randomized controlled trials to produce weight loss are listed in Box II.


II –Effective Weight-Loss Interventions

If patients are not ready or able to follow comprehensive diet and physical activity recommendations, they may be counseled to follow specific interventions that may help reduce their risk of obesity or prevent further weight gain. The following interventions have been shown in randomized controlled trials to produce weight loss.

  • Reduced intake of sweetened drinks, especially carbonated drinks, fruit punches, and 100% fruit juice. Persons who drink sweetened beverages consume excess calories and will gain weight unless they compensate by reducing food intake.44 In one study of children aged 7 to 11 years, those who were taught about the risks of sweetened drinks and encouraged to increase water intake had lower rates of obesity.45 In another study, patients given sugar-sweetened drinks gained weight while those given artificially sweetened drinks lost weight over 3 weeks.46
  • Decreased television time. One study showed that third- and fourthgraders who reduced their television time demonstrated a significant decrease in body mass index, triceps skin-fold thickness, and abdominal circumference over 6 months.47 Some investigators estimate that 30% of cases of new obesity could be prevented if persons limited television viewing to less than 10 h/wk and walked briskly for 30 min/d.19
  • Consuming an ad-lib low–glycemic load diet versus a reduced-fat, reduced-calorie diet. A low–glycemic load diet consists of a high-fiber, high-bulk, and balanced (carbohydrates, proteins, and healthful fats) diet. The glycemic index measures the blood glucose response to 50 g of a carbohydrate. The glycemic load is a product of a food’s glycemic index and its carbohydrate content. One 6-month study showed that obese adolescents who ate an ad-lib low–glycemic load diet lost significantly more weight and had lower fat mass than those who followed a low-fat, calorie-restricted diet.48 Examples of low–glycemic load diets are the “Zone” diets, which have been shown to be effective at 1 year.22

Often, there are contributing factors that need to be addressed: these include psychological disorders, thyroid dysfunction, and physical limitations. Emphasize to patients that these disorders do not cause obesity but may exacerbate it.

Because most attempts at weight loss eventually fail, emphasis on risk reduction and weight maintenance, rather than purely on weight loss, is critical to long-term success. A weight loss of 10% will improve overall health and can be considered an optimal goal, but weight maintenance is more realistic and should be the initial goal.

DIET

Any successful long-term weight-loss intervention must include dietary modification and calorie restriction. Few of the numerous advertised weight-loss programs have been proved effective in high-quality studies. Very low-calorie and carbohydrate-restrictive diets (such as the Atkins diet) are effective in the short term, but dieters tend to regain much of the weight and, by 1 year, there is no significant difference among diet types.22-25

Dietary compliance is more important than the type of diet. Patients who are compliant not only lose more weight than less compliant patients but are better able to maintain weight loss over time.22 Therefore, for long-term success, patients should find a reasonable diet that they can follow for life, rather than a radical plan (such as the Atkins or Ornish diet) that is difficult to follow. Healthful diets should include an increased intake of fruits, vegetables, fiber, fish, nuts, and monounsaturated or polyunsaturated fats, and reduced consumption of trans fatty acids, refined carbohydrates, and sweetened drinks.

PHYSICAL ACTIVITY

Exercise and physical activity help a person burn calories, lose weight, and maintain weight loss. A number of studies of persons who have successfully maintained long-term weight loss show that the only common denominator is ongoing physical activity.26,27 Even a small amount of physical activity offers significant benefit, independent of weight loss. Persons who exercise regularly have lower rates of mortality, morbidity, and depression than non-exercisers, as well as an overall improvement in well-being.28 In an observational study of patients with diabetes, moderate and high levels of physical activity decreased mortality by 51% and 61%, respectively. These benefits occurred independent of weight loss.29

How much exercise is enough? The American Diabetes Association, the American Academy of Family Physicians, and the American College of Sports Medicine all recommend a minimum of 150 minutes of physical activity per week over 3 to 7 days.30-32 Generally speaking, the more frequent, prolonged, and intense the exercise, the greater the weight loss.33 Persons who burn 2200 to 2800 kcal/wk in physical activity appear to lose the most weight.34 Various types of exercise--aerobic versus weight resistance, for example--differ in the number of calories burned per hour, but this does not influence total weight loss.35

Any factor that increases compliance with an exercise regimen will improve its effectiveness. The patient might try implementing a reward system or installing a home gym. Many patients report better outcomes when they exercise with a partner or friend, or choose exercises that are individualized to their preferences and needs.36

BEHAVIOR MODIFICATION

The goal of behavior modification is to change the patient's diet and/or exercise habits. The most effective nonpharmacologic and nonsurgical obesity treatments include behavior modification in conjunction with diet and exercise.35

Behavior modification may involve counseling from a physician, nurse, dietitian, or other member of a weight-loss team. Options include individual or group counseling, support groups, cognitive-behavioral therapy, and relapse prevention. The more varied and intense the intervention, the greater the weight loss. High-intensity interventions, defined as more than 1 person-to-person visit per month during the first 3 months of a weight-loss program, are more effective than low- and moderate-intensity treatment.2 Continuing these interventions helps the patient maintain weight loss over the long term.

PHARMACOLOGIC TREATMENT

The obesity agents sibutramine( and orlistat( are reserved for patients who have a BMI of 27 kg/m2 or higher and associated comorbidities, such as diabetes or angina, or a BMI of 30 kg/m2 or higher. These medications are more effective than lifestyle changes alone and work best in combination with diet, exercise, and behavior modification.37,38

Sibutramine inhibits dopamine, norepinephrine(, and serotonin reuptake and increases satiety. Most side effects are minor, except for an increase in heart rate and blood pressure.2 Because these events are idiosyncratic, monitor heart rate and blood pressure in all patients taking sibutramine. Avoid prescribing this agent for persons with coronary heart disease.Average weight loss is 2.8 to 4.2 kg over 8 to 52 months.2

Orlistat is a GI lipase inhibitor that decreases intestinal fat absorption. Most side effects (vitamin deficiency, flatulence, stool leakage, and greasy stools) are related to malabsorption and are not serious. Weight loss with orlistat averages 3.5 kg over 1 to 2 years.2

Currently, neither orlistat nor sibutramine is approved for treatment longer than 2 years. Weight loss is maintained during treatment, but patients tend to regain the weight once treatment stops.2,37

SURGERY

Bariatric surgery is generally considered a treatment of last resort, reserved for persons with a BMI of 35 kg/m2 or higher plus serious comorbidities, or a BMI of 40 kg/m2 or higher. By these criteria, 5% to 6% of the American adult population is eligible for bariatric surgery.39

Types of procedures. The most commonly performed procedures reduce gastric capacity, induce malabsorption by shortening the effective length of the small intestine, or both. Vertical banded gastroplasty (VBG) and gastric banding are examples of purely restrictive procedures. Jejunoileal bypass was the most common malabsorption procedure but has largely been abandoned because of the development of severe protein- calorie malnutrition and cirrhosis.

The most frequently performed combination surgery is the Roux-en-Y gastric bypass, in which a 20-mL gastric pouch is constructed and connected to a variable-length Roux limb to bypass much of the small intestine.

Weight loss with bariatric surgery averages 23 to 28 kg at 2 years and 16.1 kg at 10 years.39,40 A recent meta-analysis estimated that the average patient loses 61% of his excess body weight.41 In general, patients lose more weight after gastric bypass than after VBG or gastric banding.

All 3 procedures can be performed laparoscopically. Laparoscopic techniques are associated with decreased morbidity, shorter hospital stays, fewer ICU admissions, and less blood loss. However, laparoscopic surgeries last longer than open surgeries (225 vs 100 minutes).2

Risks of surgery. Bariatric surgery is associated with a mortality rate of 1% or less, usually related to postoperative pulmonary embolism or early leakage from intestinal anastomoses. Wound infections are the most common short-term complication and may occur in up to 20% of patients.42 Vitamin deficiencies and loose, frequent stools are possible long-term effects. Patients who undergo restrictive procedures may also have symptoms attributable to decreased stomach size, such as acid reflux and vomiting. Although complication rates are slightly lower with VBG and gastric banding, up to 20% of these surgeries are later converted to gastric bypass because patients do not lose enough weight.2 It is important to collaborate with the surgeon to monitor long-term risk factors as well as weight loss.

Benefits of surgery. In properly selected patients, bariatric surgery is very effective. Patients also have a significant amelioration of cardiovascular risk markers, including hypertension, diabetes, hypertriglyceridemia, and low high-density lipoprotein cholesterol levels, at 10 years after surgery.43


CLINICAL HIGHLIGHTS

  • A sedentary lifestyle, improper diet, and excess calorie intake increase the risk of obesity in children, teenagers, and adults. Additional risk factors for adolescents include consumption of fast-food meals and smoking.
  • For long-term success, patients should find a reasonable diet that they can follow for life, rather than a radical plan that may be effective in the short term but that is difficult to adhere to for the long term.
  • Even small amounts of physical activity offer significant benefits—including lower rates of morbidity, mortality, and depression--independent of weight loss.
  • The most effective obesity treatments include behavior modification—such as counseling from a physician, nurse, or dietitian--in conjunction with diet and exercise.
  • Specific interventions that have proved helpful for overweight persons include reducing or eliminating consumption of sweetened drinks, becoming more physically active, and following a low-glycemic load diet that includes whole grains, fiber, and nuts.
References

1. Newman C. Why are we so fat? Natl Geogr Mag. 2004;s206(2):46-59.
2. McTigue KM, Harris R, Hemphilll B, et al. Screening and interventions for obesity in adults: summary of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2003;139: 933-966.
3.
Bray GA, Neilson SJ, Popkin BM. Consumption of high fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr. 2004;79:537-543.
4.
American Cancer Society. Cancer prevention and early detection facts and figures, 2005. Available at: http://www.cancer.org. Accessed December 19, 2005.
5. Strauss RS, Pollack HA. Epidemic increase in childhood overweight, 1986-1998. JAMA. 2001;286: 2845-2848.
6.
Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: public-health crisis, common sense cure. Lancet. 2002;360:473-482.
7.
Fontaine KR, Redden DT, Wang C, et al. Years of life lost due to obesity. JAMA. 2003;289:187-193.
8.
Olshansky SJ, Passaro DJ, Hershow RC, et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005;352: 1138-1145.
9.
Wideroe M, Vik T, Jacobsen G, Bakketeig LS. Does maternal smoking during pregnancy cause childhood obesity? Paediatr Perinat Epidemiol. 2003; 17:171-179.
10.
Whitaker RC, Dietz WH. Role of the prenatal environment in the development of obesity. J Pediatr. 1998;132:768-776.
11.
Laitinen J, Power C, Jarvelin MR. Family social class, maternal body mass index, childhood mass index, and age at menarche as predictors of adult obesity. Am J Clin Nutr. 2001;74:287-294.
12.
Crespo CJ, Smit E, Troiano RP, et al. Television watching, energy intake, and obesity in US children: results from the third national health and nutrition examination survey, 1988-1994. Arch Pediatr Adolesc Med. 2001;155:360-365.
13.
Coon KA, Goldberg J, Rogers BL, Tucker KL. Relationship between use of television during meals and children's food consumption patterns. Pediatrics. 2001;107:E7.
14.
Cavdini C, Seiga-Riz AM, Popkin BM. US adolescent food intake trends from 1965 to 1996. Arch Dis Child. 2000;83:18-24.
15.
Giammattei J, Blix G, Marshak HH, et al. Television watching and soft drink consumption: associations with obesity in 11- to 13-year-old schoolchildren. Arch Pediatr Adolesc Med. 2003;157:882-886.
16.
Committee on Nutrition. Prevention of pediatric overweight and obesity. Pediatrics. 2003;112:424-430.
17.
Liu S, Willett WC, Manson JE, et al. Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr. 2003;78:920-927.
18.
Sabate J. Nut consumption and body weight. Am J Clin Nutr. 2003;78:647S-650S.
19.
Hu FB, Li TY, Colditz GA, et al. Television watching and other sedentary behaviors in relation to risk of obesity in type 2 diabetes mellitus in women. JAMA. 2003;289:1785-1791.
20.
Calle EE, Thun MJ, Petrelli JM, et al. Body-mass index and mortality in a prospective cohort of US adults. N Engl J Med. 1999;341:1097-1105.
21.
Centers for Disease Control and Prevention. BMI: Body Mass Index.Available at: http://www. cdc.gov/nccdphp/dna/bmi. Accessed October 24, 2005.
22.
Dansinger ML, Gleason JA, Griffith JL, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005;293:43-53.
23.
Pirozzo S, Summerbell C, Cameron C, et al. Advice on low-fat diets for obesity. Cochrane Database Syst Rev. 2002;(2):CD003640.
24. Hong K, Li Z, Wang HJ, et al. Analysis of weight loss outcomes using VLCD in black and white overweight and obese women with metabolic syndrome. Int J Obes (Lond). 2005;29:436-442.
25.
Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of low-carbohydrate diet for obesity. N Engl J Med. 2003;348:2082-2090.
26.
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.
27. Klem ML, Wing RR, McGuire MT, et al. A descriptive study of individuals successful at long-term maintenance of substantial weight loss. Am J Clin Nutr. 1997;66:239-246.
28.
Fletcher GF, Balady G, Blair SN, et al. Statement on exercise: benefits and recommendations for all programs for all Americans. A statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation. 1996;94:857-862.
29.
Hu G, Jousilahti P, Barengo NC, et al. Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes. Diabetes Care. 2005;28:799-805.
30.
American Diabetes Association. Clinical practice recommendations. Available at: http://www. diabetes.org/for-health-professionals-and scientists/ cpr.jsp. Accessed December 19, 2005.
31.
Morey SS. ACSM revises guidelines for exer-cise to maintain fitness. Am Fam Physician. 1999;59:473.
32. familydoctor.org. Nutrition and exercise: healthy balance for a healthy heart. Available at: http://www.familydoctor.org/288.xml. Accessed December 19, 2005.
33.
Jeffery RW, Wing RR, Sherwood NE, et al. Physical activity and weight loss: does prescribing higher activity goals improve outcomes? Am J Clin Nutr. 2003;78:684-689.
34.
Schoeller D. But how much physical activity? Am J Clin Nutr. 2003;78:669-670.
35.
Knowler WC, Barrett-Conner E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
36. Jakicic JM, Winters C, Lang W, Wing RR. Effects of intermittent exercise and use of home exercise equipment on adherence, weight loss, and fitness in overweight women: a randomized trial. JAMA. 1999;282:1554-1560.
37.
Wirth A, Krause J. Long-term weight loss with sibutramine: a randomized controlled trial. JAMA. 2001;286:1331-1339.
38.
Karhunen L, Franssila-Kallunki A, Rissanen P, et al. Effect of orlistat treatment on body composition and resting energy expenditure during a two-year weight-reduction programme in obese Finns. Int J Obes Relat Metab Disord. 2000;24:1567-1572.
39.
Must A, Spadano J, Coakley EH, et al. The disease burden associated with overweight and obesity. JAMA. 1999;282:1523-1529.
40. Colquitt J, Clegg A, Sidhu M, et al. Surgery for morbid obesity. Cochrane Database Syst Rev. 2003; (2):CD003641.
41.
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systemic review and meta-analysis. JAMA. 2004;292:1724-1737.
42.
Christou NV, Jarand J, Sylvestre JL, McLean AP. Analysis of the incidence and risk factor for wound infections in open bariatric surgery. Obes Surg. 2004;14:16-22.
43.
Sjostrom L, Lingroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004; 351:2683-2693.
44.
James J, Thomas P, Cavan D, Kerr D. Preventing childhood obesity by reducing consumption of carbonated drinks: cluster randomised controlled trial. BMJ. 2004;328:1237.
45.
Mattes RD. Dietary compensation by humans for supplemental energy provided as ethanol or carbohydrate in fluids. Physiol Behav. 1996;59:179-187.
46.
Decastro JM. The effects of spontaneous ingestion of particular foods or beverages on the meal pattern and overall nutrient intake of humans. Physiol Behav. 1993;53:1133-1144.
47.
Robinson TN. Reducing children's television viewing to prevent obesity: a randomized controlled trial. JAMA. 1999;282:1561-1567.
48.
Ebbeling CB, Leidig MM, Sinclair KB, et al. A reduced-glycemic load diet in the treatment of adolescent obesity. Arch Pediatr Adolesc Med. 2003; 157:773-779.