N u t r i t i o n In t e r v e n t i o n s f o r

Obesity
a, b c
Jamy D. Ard, MD *, Gary Miller, PhD , Scott Kahan, MD, MPH

KEYWORDS
 Obesity  Dietary therapy  Energy balance  Weight loss
 Maintenance of weight loss  Weight-reducing diet

KEY POINTS
 Obesity is a complex, chronic disease that requires a period of negative energy deficit fol-
lowed by restoration of energy balance to successfully reduce body weight.
 Multiple dietary strategies have been shown to be effective for reducing body weight. The
particular components of the dietary strategy, including macronutrient balance, amount of
energy deficit, and foods/food types, can have an impact on adherence and comorbid risk
factors.
 Maintenance of weight loss of 3% or more of body weight can lead to significant improve-
ments in risk factors. Specific guidance should be provided on strategies that are most
effective for weight loss maintenance to help sustain risk factor improvements and reduce
body weight.

INTRODUCTION

Obesity is among the most prevalent chronic diseases in the United States and much
of the world, contributing to substantial morbidity, mortality, and health care expendi-
tures. Nearly every health care professional has to manage obesity or comorbid con-
ditions related to obesity. The most recent NHANES (National Health and Nutrition
Examination Survey) data show that 36.5% of American adults fit the definition of
obesity.1 Prevalence of obesity is significantly higher in certain subgroups, with His-
panic Americans and African Americans having rates of 42.5% and 47.8%, respec-
tively.2 Globally, approximately 600 million people have obesity, with more of the
world’s inhabitants overweight than underweight, and most of the world’s population
living in countries where overweight and obesity cause more deaths than
underweight.3

a
Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston
Salem, NC, USA; b Department of Health and Exercise Science, Wake Forest University, Winston
Salem, NC, USA; c Department of Health Policy and Management, Milken Institute School of
Public Health, George Washington University, Washington, DC, USA
* Corresponding author.
E-mail address: [email protected]

Med Clin N Am 100 (2016) 1341–1356

http://dx.doi.org/10.1016/j.mcna.2016.06.012 medical.theclinics.com
0025-7125/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
1342 Ard et al

Although the causes of obesity are multifactorial, the common pathway is a sus-
tained state of positive energy balance, leading to an increase in fat mass. The excess
accumulation and storage of adipose tissue that defines obesity leads to a wide array
of comorbid conditions. To successfully treat obesity, the primary tenet of nutrition
therapy is to create a negative energy balance, leading to reduction of fat stores
that are being used as a source of energy. Weight loss of 3% or more of body weight
can lead to clinically meaningful improvements in risk factors associated with obesity.
This article provides an overview of obesity and its classification, dietary strategies for
treatment, expected outcomes and challenges, and considerations for successful
maintenance of weight loss. It discusses specific nutrition considerations for patients
with obesity and common comorbid conditions, and addresses several popular claims
for diets and weight loss supplements.

Background and Classification

Obesity is a condition of excess accumulation and storage of adipose tissue, which is
a metabolically active tissue that has many bodily functions in addition to energy stor-
age, including hormone synthesis and thermoregulation. Obesity is associated with
nearly 200 comorbid conditions, including cardiometabolic disorders (eg, type 2 dia-
betes, cardiovascular disease, hypertension, dyslipidemia), gastrointestinal disorders
(eg, gallbladder disease, pancreatitis, esophageal reflux), mechanical disorders (eg,
osteoarthritis of weight-bearing joints, hypoventilation), numerous cancers, and
mental health conditions (eg, depression), as well as functional limitations and
decreased health-related quality of life.4
Obesity is most commonly defined by body mass index (BMI; body weight [kg
[/height [meters] squared) greater than or equal to 30 kg/m2. For adults, a normal
BMI is defined as 18.5 to 25 kg/m2, overweight as BMI 25 to 29.9 kg/m2, and obesity
as BMI greater than or equal to 30 kg/m2, with severe obesity defined as BMI greater
than or equal to 40 kg/m2 (Table 1). BMI is highly correlated with total body fat, based
on studies of body composition using various techniques in the general population,
and is positively associated with morbidity and mortality.5–7 However, BMI has several
limitations. First, BMI does not distinguish fat from lean mass. BMI can underestimate
body fat in older adults, because people tend to lose lean mass and accumulate fat
mass with age; conversely, very lean individuals with high muscle mass, such as highly
trained athletes, have less body fat than predicted by calculated BMI.8 Next, as with
any attempt to categorize a continuous phenomenon, the association with other dis-
ease risks in the lower ranges of abnormal BMI (ie, overweight) are not as consistent
on an individual level.7 In addition, BMI does not account for body fat distribution,
which can alter risk associations. Visceral adipose tissue, most commonly found in

Table 1
BMI classification

Weight Classification BMI (kg/m2)

Underweight <18.5
Normal weight 18.5–24.9
Overweight 25–29.9
Obesity class 1 30–34.9
Obesity class 2 35–39.9
Obesity class 3 401
 Nutrition Interventions for Obesity 1343

truncal/abdominal obesity, is metabolically active tissue and a promoter of systemic

inflammation and insulin resistance via secretion of adipokines, which increases risk
for cardiovascular disease, type 2 diabetes, and carcinogenesis.9,10 Subcutaneous
fat accumulation is generally associated with lower metabolic risk, although some ev-
idence suggests that subcutaneous fat accumulation in the abdominal area may
contribute to insulin resistance and inflammation.11,12
Several proposed obesity classifications combine anthropometric and clinical
criteria to define obesity and obesity risk. These staging systems, such as the Edmon-
ton Obesity Staging System and the American Association of Clinical Endocrinologists
staging algorithm, include obesity comorbid conditions and functional limitations to
provide a broader classification scheme of obesity13,14 (Table 2). Preliminary data
suggest that staging systems may have higher correlation with morbidity and mortality
risk, compared with BMI alone, and therefore may aid clinicians in determining appro-
priate intensity of treatment strategies for each individual (ie, patients with higher
stages of obesity are likely to be at greater risk of morbidity and mortality from
obesity and thus may be more appropriate candidates for aggressive obesity treat-
ment modalities, compared with lower stage patients), although further research is
necessary.15

DIETARY STRATEGIES FOR OBESITY TREATMENT

Creating an Energy Deficit
Weight loss requires inducing and sustaining a state in which total energy expenditure
is greater than energy intake (ie, an energy deficit), resulting in the use of stored fat as a
source of energy. Although this principle is often communicated to patients in a mes-
sage of eat less and exercise more, understanding the multifactorial contributions to
weight gain and the rationale and nuances of evidence-based strategies can lead to
more effective treatment and counseling. This article focuses on nutritional contribu-
tions to energy balance and other nutritional considerations for obesity management.
In adults, the primary components for total daily energy expenditure (TDEE) include
resting metabolic rate (RMR), energy expenditure of activity (AEE), and thermic effect
of food (TEF). For sedentary individuals, RMR represents roughly two-thirds of TDEE

Table 2
Edmonton Obesity Staging System

Obesity-related Physical Obesity-related Mental

Obesity-related Medical Symptoms/Comorbidities Health or Psychosocial
Stage Risk Factors/Comorbidities or Functional Limitations Symptoms/Comorbidities
0 None None None
1 Mild/subclinical (eg, Mild (eg, fatigue, dyspnea Mild
borderline hypertension, on exertion)
IFG)
2 Established (eg, Moderate Moderate
hypertension, type 2
diabetes)
3 End-organ damage (eg, Significant Significant
CAD, CHF)
4 Severe/end stage Severe Severe

Abbreviations: CAD, coronary artery disease; CHF, congestive heart failure; IFG, impaired fasting
glucose.
1344 Ard et al

with AEE comprising 15% to 25% and the TEF contributing w8% of TDEE. The energy
balance equation is a thermodynamic process that incorporates both TDEE and en-
ergy intake. With a sustained positive balance (ie, energy intake greater than energy
expenditure), overweight and obesity develop. In contrast, a prolonged negative en-
ergy balance with energy expenditure being greater than energy intake changes the
energy balance to negative and leads to weight loss.
Reducing daily energy intake to create an energy deficit can be accomplished
through several types of dietary changes. These changes include reducing portion
sizes, using meal replacement products to reduce dietary choice and caloric intake,
choosing more nutrient-dense and less energy-dense foods, or altering macronutrient
composition, glycemic index/load, meal frequency, or eating pattern. Controlling
portion sizes is often achieved through use of prepackaged foods, such as meal re-
placements. Prepackaged foods are commonly in the form of shakes or bars, but
may also include meals of whole foods that are allocated in set portions (eg, frozen
meals or preprepared meals). These foods are regularly promoted as a low-calorie
product and several studies have shown their effectiveness for weight loss.16–18
Altering food choices to limit high-energy foods, such as sugar-sweetened beverages
and high-fat and high-sugar baked goods, and replacing these with foods that are
lower in energy and higher in micronutrients, water, and fiber increases satiety and re-
duces energy density. The notion that humans eat a certain volume of food, indepen-
dent of total energy content, led to the strategy to increase food volume through
reducing energy density.19–21 In the short term, consuming a food with a low energy
density, such as soup or salad, before a meal reduces total energy intake for a single
meal and for multiple meals when consumed over 1 to 2 days.22–25 Furthermore, coun-
seling to reduce energy density through increasing fruit and vegetable intake, along
with decreasing fat intake, showed greater weight loss than was seen in a group
that was only instructed on reducing fat intake.26 This evidence formed the basis for
the 2010 Dietary Guidelines recommendation to follow an eating pattern with a low en-
ergy density to manage body weight.

The role of macronutrients and other dietary factors

Unique combinations of macronutrient levels are often prescribed for weight loss.
Because proteins, carbohydrates, and lipids have different effects on energy meta-
bolism, appetite, and satiety, it is intuitive to consider that altering the proportion of
macronutrients in diets with similar total calories will cause weight loss and body
composition changes. Furthermore, the energy density of the diet may be changed
in isocaloric diets differing in macronutrient composition. Because of the finite capac-
ity for storing protein and carbohydrate in the body, and the nearly limitless capacity
for fat storage, the body must have an ability to acutely regulate protein and carbohy-
drate balance.27 How dietary macronutrient content affects the body’s energy balance
depends to some extent on the energy state of the body (ie, in a negative, positive, or
neutral energy balance). In carefully controlled feeding studies, there is no significant
difference in weight loss when reducing fat or carbohydrate content of the diet as long
as there is similar total energy reduction. In contrast, during ad libitum intake, there are
differences in weight loss between high-fat versus low-fat diets.28–30 This difference is
attributed to the higher diet-induced thermogenesis and lower energy intake with car-
bohydrates and proteins versus fat.31,32
Manipulating dietary protein levels (25%–35% of energy as protein) has been
favored as a dietary strategy for weight loss and post–weight-loss regain. High-
protein diets are thought to increase diet-induced thermogenesis, as well as reduce
energy intake through altering satiety hormones, both of which promote a negative
 Nutrition Interventions for Obesity 1345

energy balance.33–36 In ecological studies and randomized controlled trials, high-

protein diets have favorable weight management outcomes.37–40 However, clinically
meaningful weight loss can occur across a broad range of macronutrient composi-
tions, particularly varying proportions of carbohydrates and fats, which are the most
commonly varied among dietary recommendations and claims.41 In a study that
examined 4 diets that varied in content of fat (20%–40%), protein (15%–25%), and
carbohydrates (35%–65%), there was similar weight loss among the interventions
over a 2-year period. There were no differences in hunger and satiety ratings for all
diets.
It is well known that there is a wide interindividual variation in weight loss between di-
etary strategies. The variation in response can potentially be mitigated by identifying fac-
tors that modify the effect of a given dietary intervention. For example, evidence from
subgroup analyses suggests that the weight loss response on high-carbohydrate or
low-carbohydrate diets is related to insulin sensitivity, with a better response seen
with a low-carbohydrate versus a high-carbohydrate diet in insulin-resistant, but not
insulin-sensitive, individuals.42–44 Despite these findings, most of the current evidence
suggests that the average weight loss responses to a wide range of dietary macronu-
trient patterns and other dietary manipulations are similar and generally a function of
compliance and the energy restriction achieved.7 One relevant example based on the
recent popularization of the concept is the use of low-glycemic-index/low-glycemic-
load diets for weight loss. Low-glycemic-index foods produce a lesser and more gradual
increase in blood glucose levels, leading to less stimulation of insulin secretion.45 Glyce-
mic load is calculated as the total carbohydrate of the food (grams) multiplied by the gly-
cemic index value of the food divided by 100. One of the CALERIE (Comprehensive
Assessment of Long term Effects of Reducing Intake of Energy) trials assessed a
high-glycemic-load diet compared with a low glycemic load diet in the setting of a
30% calorie restriction.46 After a feeding period of 6 months, both groups self-
administered assigned dietary plans for an additional 6 months. There were no differ-
ences in weight loss at 12 months for both groups (8% for high vs 7.8% for low).46 Future
research needs to address variable responses in the setting of different diet composi-
tions and nutrient profiles, and in different genetic and biological makeups.
Ultimately, the future direction of obesity intervention will be to prescribe personal-
ized nutrient profiles to match the specific needs of individual patients. Interindividual
responses to specific foods create an opportunity to design prescriptions that lead to
optimized outcomes compared with general guidelines.47 The targets for individuali-
zation could include specific dietary patterns (eg, low glycemic load or decreased
sugar intake), exclusion of certain nutrients (eg, gluten), specific dietary supplements,
nutritional alteration of the microbiome, or consideration of biological factors (eg, de-
gree of insulin sensitivity). Because the targets involved in energy homeostasis are
myriad, the keys to unlocking the interaction between the nutrient environment and
energy balance may ultimately include genotyping, metabolomics, and proteomics
to direct nutrient therapy. However, these concepts are currently in the domain of po-
tential future use as research and technology improve. At present, the most promising
nutrition consideration for obesity is managing energy balance.

MODIFYING DIET COMPOSITION TO ADDRESS ASSOCIATED RISK FACTORS

Dietary patterns and compositions can be used to address specific cardiometabolic

risk factors in the context of a weight-reducing diet. In this manner, a specific dietary
pattern leads to a specific type of response in the cardiometabolic profile, allowing
targeted intervention. For example, a low-carbohydrate, high-fat diet has been
1346 Ard et al

associated with significant improvements in triglycerides, high-density lipoprotein

cholesterol, and blood glucose levels in people with type 2 diabetes.48,49 The DASH
(Dietary Approaches to Stop Hypertension) dietary pattern, which features high in-
takes of fruits, vegetables, low-fat dairy, and whole grains, has been used as the basis
of a weight reduction diet targeted for people with greater than normal blood pressure
and stage I hypertension. In the Pounds Lost clinical trial, specific patterns of improve-
ments in cardiometabolic risk factors were evident across 4 diets that varied in fat
(20%–40%), protein (15%–25%), and carbohydrate (35%–65%) content.41 The high-
est carbohydrate diet had the greatest decrease in low-density lipoprotein level,
whereas the lowest carbohydrate diet had the greatest increase in high-density lipo-
protein level. The high-protein diet had the largest decrease in fasting serum insulin
level. Consistent with these results, Shai and colleagues50 showed improvements in
blood lipids with low-fat and low-carbohydrate dietary interventions, but the low-
carbohydrate diet had a greater reduction in the ratio between total cholesterol and
high-density lipoprotein. Note that they also found more favorable cardiometabolic ef-
fects in individuals with diabetes in patients on a Mediterranean diet pattern versus
low-fat diet. Thus, specific dietary recommendations may have more to do with goals
for improvements in obesity-associated comorbid conditions than any expected dif-
ferences in average weight loss from the dietary pattern.
Consistent with these results, most weight loss claims of popular diets are unsub-
stantiated, as was recently codified by the obesity management guidelines led by
the National Heart, Lung, and Blood Institute and published jointly by the American
Heart Association, American College of Cardiology, and The Obesity Society.7 As
part of an in-depth systematic review process, a key question was included about
which is the best diet for weight loss. Seventeen popular diets were reviewed,
including the American Heart Association Step 1, ADA diet, low-carbohydrate and
Atkins-type diets, low-fat diets, low-glycemic-index diets, vegetarian and vegan diets,
DASH diets, Zone diets, and Mediterranean diets. There was no clearly superior die-
tary approach, beyond finding a pattern that leads to moderately reduced caloric
intake. Importantly, the guidelines recommend respecting patients’ preferences;
thus, personal preference, rather than diet claims, are a key factor in macronutrient di-
etary prescription. Moreover, generally healthful dietary recommendations, and elim-
inating or minimizing sugar-sweetened beverages, should be considered for any
dietary approach.

PROMOTING ADHERENCE WITH AN APPROPRIATE DIETARY PRESCRIPTION

Overall, trials comparing a wide variety of macronutrient distributions have found

weight loss success in nearly all types of hypocaloric diets.51 This finding suggests
adherence to a reduced energy diet as the main driving force for weight loss suc-
cess.41,52,53 Thus, finding a diet that is palatable and fits with the lifestyle of the
individual is a key to effective weight loss. For some, this may be achieved with a
high-carbohydrate diet, whereas others may prefer a high-fat or high-protein diet.
This approach is consistent with the Pounds Lost findings, by Sacks and colleagues,41
discussed earlier, which showed that adhering to the macronutrient intake goal with a
hypocaloric diet was associated with increased weight loss. In this study, group
means for satisfaction with the diet, as well as satiety and hunger, were not different
across 4 groups that had different target intakes for protein, fat, and carbohydrates.
Importantly, there was a loss in dietary adherence over the 1-year follow-up period,
showing the difficulty in long-term adherence to a dietary plan that is different from
the person’s habitual diet.
 Nutrition Interventions for Obesity 1347

EXPECTED WEIGHT LOSS OUTCOMES

Similar to the management of many other chronic diseases, the goal of obesity treat-
ment is to improve health and long-term risk, not necessarily to rid the body of obesity
(eg, a treatment goal of diabetes management is to improve glycemic control to
achieve a hemoglobin A1c level <7%, not necessarily to achieve a normal hemoglobin
A1c level). There is strong evidence for health and comorbidity improvement with
small weight losses. Sustained weight loss of 3% to 5% of initial body weight is likely
to improve triglyceride levels, glycemic control, and risk of developing type 2 dia-
betes.7 Sustained loss of 5% to 10% of initial body weight generally ameliorates or im-
proves numerous other comorbid conditions and risk factors (eg, blood pressure,
hepatic steatosis, urinary incontinence), although improvements in some risk factors
and obesity-associated conditions (eg, low-density lipoprotein [LDL] cholesterol,
sleep apnea, nonalcoholic steatohepatitis) may require greater weight losses for
meaningful clinical improvement.7,54–56
As described earlier, reduction of body fat is accomplished by negative energy bal-
ance via changes in energy intake or expenditure. Expected rate of weight loss is tradi-
tionally estimated by reduced energy intake and/or increased energy expenditure by
3500 kcal to lose 450 g (1 pound). Thus, a 500 kcal/d energy deficit would theoretically
lead to 450 g/wk of body weight loss. However, this general rule does not account for
dynamic physiologic adaptations during weight loss, such as alterations in resting en-
ergy expenditure and increased muscle efficiency, thereby overestimating weight loss
results.
These compensatory adaptations make evolutionary sense in that they counter sus-
tained negative energy balance related to famine. More complex mathematical
models have been developed that account for these metabolic adjustments during
negative energy balance. In one such model, Hall and colleagues57 predict greater
than 10 kg difference in weight loss using the static linear model of the 3500-kcal
rule versus their dynamic model, which incorporates energy expenditure changes
with weight loss. Thus, when using the 3500-kcal/450 g value, patients typically expe-
rience less rapid weight loss and may fail to reach their expected weight loss goals,
even for those strictly adhering to their target behavioral goals. On average, weight
losses of up to 8 kg have been observed at 1 year in behavioral interventions that
include a prescribed energy deficit diet combined with frequent behavioral counseling
and a prescription for increased physical activity.7 The weight loss nadir is generally
observed at about 6 months of intervention with maintenance of weight loss achieved
with continued intervention through 12 months. The nadir at 6 months is commonly
observed as a weight loss plateau, and is, in part, attributed to these metabolic adap-
tations to energy expenditure in the setting of persistent low energy intake.
In light of these physiologic adaptations that occur with weight loss, in addition to
the obesogenic environment that makes sustained decreases in dietary intake difficult
to maintain over long periods, it is important to manage expectations and communi-
cate realistic expectations for both the rate of expected weight loss and long-term
weight loss goals. Several studies of individuals beginning weight loss programs
show that weight loss expectations wildly exceed what is realistic. For example, in
one study of 60 patients beginning a clinical trial of behavioral weight loss, subjects
reported mean goal weight loss of 33% of initial body weight; an amount that exceeds
the average weight loss with bariatric surgery.58 At a minimum, health care providers
should proactively work with patients to negotiate realistic weight loss and behavioral
goals, informed by the type of strategy used (eg, very-low-calorie diets [VLCDs] using
meal replacement products generally lead to faster initial rates of weight loss, whereas
1348 Ard et al

a food-based deficit diet may require a longer period to achieve a similar weight loss)
and life circumstances (ie, realistic weight loss may be lower during periods of life tran-
sition, such as job changes). Importantly, goal setting should include non–weight-spe-
cific goals (eg, improvements in physical functioning, risk factors, quality-of-life
indices).

TROUBLESHOOTING AND COMMON COMPLICATIONS

Limited Weight Loss
Patients with less than their expected weight loss are a challenging consideration. The
clinician’s role is to systematically review key components of the intervention, with the
goal of reinforcing consistent use of evidence-based tools that are effective for pro-
moting sustained adherence to behaviors that promote a negative energy balance.
With any behavioral intervention, it can be expected that the level of engagement
and degree of adherence will decline over time on average.59 However, brief and
focused interactions can help patients refocus efforts and lead to modifications in
the prescription that enhance weight loss.
Self-monitoring is the most common tool that can be easily used to help identify de-
viations from the dietary prescription or areas for adjustment. Patients should gener-
ally be encouraged to self-monitor dietary intake on a daily basis because this is one of
the behaviors that are most commonly associated with achieving clinically meaningful
weight loss.60 A brief review of 1 to 2 weeks of food records can help the clinician iden-
tify deviations that might not be readily obvious to the patient. Deviations most often
seen in clinical practice include skipping prescribed meals and snacks, longer inter-
vals between eating episodes, and incorrect diet composition. A more thorough re-
view can also reveal inadequate portion control and underestimation of calorie intake.
When none of these common patterns of deviation from the prescribed dietary
intake is obvious, refining the dietary prescription may be necessary. Decreasing
the calorie prescription is often the first consideration. Other than reducing portion
sizes or eating episodes, calories can often be reduced by using meal replacements
or substituting less-energy-dense food options for more-calorie-dense foods (eg,
whole fruit for dried fruit snacks). These options preserve the nutrient density of the
prescription while allowing maintenance of satiation. Altering macronutrient balance
is a second level of adjustment that can be attempted in cases of limited weight
loss. The food record can be the basis for making this adjustment; clinicians can
recommend changes that are substantively different from the current macronutrient
intake that is resulting in limited weight loss. For example, the clinician could recom-
mend that a patient shift approximately 10% of calories from the group that represents
the highest percentage of calorie intake into 2 other macronutrient groups (eg, shift
10% of carbohydrate calories into lean protein and unsaturated fat).

Weight Loss Plateau

As noted previously, many behavioral interventions for obesity have a weight loss
nadir at approximately 6 months. When patients report maintenance of behaviors
that previously resulted in weight loss but are no longer able to achieve reductions
in weight, this represents a weight loss plateau. At this point, the negative energy bal-
ance is diminished largely because of metabolic adaptations in energy expenditure
resulting from the previously discussed compensatory mechanisms designed to pro-
tect against loss of body mass. RMR decreases substantially with energy restriction,
and, because it is the largest component of TDEE, this has a significant effect on the
resulting energy balance.61–63 RMR declines as body mass decreases, because less
 Nutrition Interventions for Obesity 1349

energy is required for movement and maintenance. Furthermore, the decrease in RMR
with weight loss can be attributed to alterations in hormones and the autonomic ner-
vous system that conserve energy. Energy restriction also reduces physical activity
energy expenditure in weight-dependent activities, resulting in fewer calories burned
for a given task.61 For example, a 100-kg patient who previously burned 100 calories
when walking 1.6 km (1 mile) would now burn fewer calories after a 10% weight reduc-
tion because of improved exercise efficiency and decreased workload.

Basic Considerations for Dealing with a Weight Loss Plateau

Many of the same techniques used to address limited weight loss can also be imple-
mented to help patients work through a weight loss plateau (eg, altering macronutrient
balance, portion controls, meal replacements). Ultimately, the goal is to find the new
combination of energy intake and activity energy expenditure that leads to an energy
deficit that is sufficient to resume weight loss. Although further calorie restriction may
seem an obvious target, this strategy has limitations. Further reduction of calories may
only force more aggressive adaptation at this point, sending signals to the brain that
the low-calorie environment is persistent and even more severe. Alternatively, clini-
cians typically elect to increase calories in small increments (w100 calories/d) along
with alterations in the exercise program that circumvent the efficiencies recently
gained with ongoing training. This approach leads to a higher energy flux state, which
has been hypothesized to be more favorable for allowing expenditure of stored excess
energy as heat; the primary adaptation that is altered in the weight loss plateau.64

Risks Associated with Weight Reduction Strategies

Although the benefits of weight reduction generally outweigh the risks, clinicians
should be aware of potential complications and advise patients when precautions
are necessary. Rapid weight loss, defined as greater than 1.5 kg/wk, has been asso-
ciated with an increased risk of symptomatic gallstones.65 VLCDs (ie, <800 kcal/d),
which are associated with higher rates of weight loss, were thought to lead to gall-
stones in 10% to 25% of participants.66 The largest report to date of 3320 consecu-
tively enrolled patients in a VLCD commercial weight-loss program in Sweden showed
that the incidence of gallstones was higher compared with matched controls on a low-
calorie diet (LCD), but that the overall risk of gallstones requiring hospital care was low
(152 per 10,000 person years for the VLCD compared with 44 for the LCD).67 Differ-
ences in contemporary rates of symptomatic gallstones in people attempting to
lose weight may be a result of higher dietary fat intakes in many modern weight loss
strategies relative to the very low fat intakes that dominated in the 1980s and
1990s. These very low fat intakes may have contributed to bile stasis because fat
intake decreased below a threshold needed to stimulate gallbladder contraction.68
Other medical concerns that are seen more frequently in high-risk patients include
symptoms, such hypoglycemia and hypotension, resulting from the overtreatment of
comorbid conditions. Individuals with type 2 diabetes and hypertension are at risk for
adverse events if medication management is not done expectantly. Individuals on in-
sulin or oral hypoglycemics such as sulfonylureas should have medications adjusted
based on initial level of glycemic control and degree of calorie restriction. Antihyper-
tensive medications can lead to postural hypotension along with symptoms of light-
headedness and dizziness if blood pressure decreases in response to the weight
reduction intervention. In addition, antihypertensive regimens with significant
amounts of diuretics can increase the risk of dehydration in patients with more rapid
weight loss responses to calorie restriction, especially if sodium intake is decreased
concomitantly.
1350 Ard et al

Less serious but more commonly occurring side effects of weight loss and reduced
calorie intake can include hair loss, changes in bowel patterns and habits, muscle
cramping, and fatigue. Hair loss is generally a function of the duration and intensity
of exposure to a low calorie intake. This type of hair loss, known as telogen effluvium,
is a reactive response to lower energy intake and generally recovers spontaneously
within 6 months of restoring energy balance (ie, during maintenance).69 Changes in
bowel habits are typically associated with changes in dietary fiber content and can
be mitigated by supplementing fiber if the dietary plan is lower (eg, a lower-
carbohydrate dietary plan). Cramping and fatigue are often related and can be asso-
ciated with minor electrolyte disturbances such as low levels of sodium, calcium, or
magnesium. These symptoms are more likely to occur when electrolytes are not
replaced adequately after strenuous exercise routines, when the patient is taking di-
uretics, or when insensible losses are high because of warm temperatures.

WEIGHT MAINTENANCE STRATEGIES

The compensatory changes that occur in response to weight loss also make it more
challenging to maintain weight loss long term. Ultimately, successful weight loss main-
tenance is a function of engaging in a consistent pattern of increased physical activity
while maintaining a dietary pattern and energy intake that is appropriate for the new,
lower body weight.

Benefits of Physical Activity in Weight Maintenance

Metabolic benefits occur from exercise training that facilitate weight loss mainte-
nance. The preservation of lean body mass during dietary restriction is the most
commonly mentioned factor that benefits weight loss maintenance. The level of
calories burned during physical activity is related to weight loss at long-term (18–
36 months) follow-up.70,71 Women who achieved at least a 10% weight loss after
24 months of behavioral weight loss therapy reported activity energy expenditure of
1515 kcals/wk, compared with fewer than 500 kcals/wk in those achieving less than
0% to 5% weight loss at 24 months.71 The recent 2014 obesity guidelines from
American College of Cardiology/American Heart Association/The Obesity Society
also suggest that exercise reduces weight regain with VLCDs.7 These same guidelines
prescribe at least 150 minutes of aerobic physical activity per week for weight loss
with 200 to 300 min/wk for maintaining lost weight or reducing weight regain. How-
ever, most of these data are from secondary analyses from randomized controlled
trials or from observational studies and do not fully answer the question of the role
for physical activity in weight loss maintenance or the regain of lost weight. Several in-
vestigations have shown that, when programs are compared with varying combina-
tions of low or high amounts of activity and exercise intensity, there is minimal
impact on weight loss and weight loss maintenance.71,72

Role of Diet Composition in Weight Maintenance

Over the long-term, most individuals struggle with maintaining their lost weight. It has
been theorized that diet composition may be critical in weight loss maintenance.
Because the energy efficiencies of metabolic pathways vary, macronutrient content
may influence energy expenditure, as well as dietary adherence.73 This theory was
tested in a crossover feeding trial of 3 isocaloric diets that varied in fat, carbohydrate,
and glycemic load during the weight maintenance period following a 10% to 15%
weight loss in overweight and obese young adults.74 Reductions in energy expendi-
ture (RMR and TDEE) from the pre–weight-loss period baseline were greatest in a
 Nutrition Interventions for Obesity 1351

low-fat diet compared with a very-low-carbohydrate diet, with the low-glycemic-index

diet being intermediate between the two. Furthermore, leptin and triiodothyronine (T3)
levels were lowest, and insulin sensitivity was highest, in the very-low-carbohydrate
diet compared with the low-fat diet. Moreover, the differences in energy expenditure
with the diets are not from lower T3 levels, because the lowest T3 level was seen with
the diet that had the least decline in energy expenditure.
The DIOGENES (Diet, Obesity and Genes) dietary study also comprehensively stud-
ied the impact of varying protein intakes and glycemic loads on weight maintenance
following 8 weeks of weight loss induced by an 800 kcal/d diet.38 Participants were
provided with food for the first 6 months, followed by self-administered plans
supported by a dietitian for the remaining 6 months. The high-protein groups (23%–
28% of calories) regained 2 kg less at 12 months than the groups consuming
low-protein diets (10%–15% of calories).75 However, there was no consistent effect
of the assigned dietary glycemic index on maintenance of weight loss. These results
show that metabolic effects during weight loss maintenance differ based on macronu-
trient content, with protein intake showing the most consistent effects on promoting
successful weight loss maintenance.

DIETARY SUPPLEMENTS FOR WEIGHT LOSS

Dietary supplements should be mentioned in any discussion of weight interventions.

Herbal and dietary supplements for weight loss can be attractive, because they
commonly promise near-miraculous benefits, seemingly without risk. Despite
increasing sales and use of over-the-counter (OTC) weight loss products, there are
minimal, if any, data supporting benefits for weight management.76–78 Unlike US
Food and Drug Administration (FDA)–approved treatments, dietary supplements are
not required to be proved effective, and few have rigorous clinical trial evidence
assessing efficacy and safety. When scientific studies are conducted, the results
are disappointing. A 2004 systematic review of 25 clinical trials covering 10 popular
supplements showed “no evidence beyond a reasonable doubt that any specific die-
tary supplement was effective for reducing body weight.”79 A 2010 review of published
systematic reviews for 9 popular weight loss supplements concluded that none are
supported by sound evidence.80 However, there are 2 OTC options to consider for
weight management. The first is the FDA-approved OTC version of orlistat, a prescrip-
tion medication that was initially approved by the FDA in 1999. Several studies support
the utility of orlistat for long-term weight management. One study showed that orlistat
(at prescription dose of 120 mg, which is twice the dose available OTC) in combination
with a behavioral weight loss intervention based on the Diabetes Prevention Program
leads to 10% body weight loss over 1 year, maintenance of most of this weight loss
through 4 years, and 45% decreased development of diabetes.81 Various versions
of fiber supplements may also be reasonable to use as dietary supplementation.
Fiber-related supplements may support weight control by increasing satiety or slow-
ing digestion. The most commonly used fiber supplement is psyllium, which has been
shown to cause small weight losses and improvements in some cardiovascular risk
factors.82 At recommended levels, the risk of adverse effects is low.

SUMMARY

Obesity is an extremely common disorder with a complex cause. The ongoing

epidemic has spurred significant advances in the understanding of nutritional
approaches to treat obesity. Although the primary challenge is to introduce a
dietary intake that creates an energy deficit, clinicians should also consider targeted
1352 Ard et al

risk factor modification with specific manipulation of the nutrient profile of the
weight-reducing diet. These strategies are broadly effective in producing clinically sig-
nificant weight loss and associated improvements in cardiometabolic risk factors.
Future research is needed to better understand how to personalize nutrient prescrip-
tions further to promote optimal risk modification and maintenance of long-term en-
ergy balance in the weight-reduced state.

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