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Adult Weight Loss Diets
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DOI: 10.1177/0884533614550251 · Source: PubMed
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Nutrition in Clinical Practice
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DOI: 10.1177/0884533614550251
 published online 7 October 2014Nutr Clin Pract
Laura E. Matarese and Walter J. Pories
Adult Weight Loss Diets: Metabolic Effects and Outcomes
 
 
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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
Invited Review
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.
Weight Loss Diets
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 
550251 NCPXXX10.1177/0884533614550251Nutrition in Clinical PracticeMatarese et al
research-article2014
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
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
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 layliterature 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
body mass index; caloric restriction; weight loss; weight reduction programs; carbohydrate-restricted diet; fat-restricted diet; obesity; 
weight loss; glycemic index; Mediterranean diet
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2 Nutrition in Clinical Practice XX(X)
the expense of other foods with little to no supporting evi-
dence. These are commonly referred to as fad diets.
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
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.
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 
A Guide to Selecting Treatment
BMI Category
Treatment 25-26.9 27-29.9 30-34.9 35-39.9 ≥40
Diet, physical activity, 
and behavior
Appropriate
NHLBI 
Guidelines
+ + + +
Pharmacotherapy Not appropriate
With co-
morbidities + + +
Surgery Not appropriate
Not 
appropriate
With co-
morbidities +
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).
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Matarese et al 3
Table 1. Comparison of Weight Loss Diets.a
Diet Advantages Disadvantages Exercise Behavioral Modification
Very low 
carbohydrate
Atkins •• 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
•• 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
•• Encourages lifelong 
changes for sustained 
weight loss
Low glycemic Zone •• Rapid initial weight 
loss
•• Emphasis on healthy 
fats
•• High satiety value
•• Complex; 
must adhere to 
caloric ratio of 
carbohydrate, 
protein, and fats 
(40-30-30)
•• Must weigh food
•• 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; diet is designed 
to get client into “the 
Zone,” requiring a 
regimented, one-size-
fits-all method of 
eating
Low fat Ornish •• Results in significant 
weight loss
•• Extremely limited 
and difficult to 
follow
•• Poor long-term 
compliance
•• Low fat often 
resulted in 
consumption of 
increased calories
•• No specific fitness 
plan, but recommends 
gradually building 
up to 30–60 min of 
walking or other 
moderate activity each 
day.
•• Stress management
•• The choice-based 
program emphasizes 
becoming aware of 
what is eaten
 LEARN •• Results in significant 
weight loss
•• Flexible food 
choices
•• Very low fat, 
which may be 
difficult to follow 
long term
•• Includes exercise •• Intensified 
structured approach 
to health behavior 
modification with 
a focus on healthy 
eating, exercise, 
coping patterns, and 
sustained weight loss
 Weight 
Watchers
•• 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
•• Healthfulbehavior 
strategies
•• Web site offers 
articles to help avoid 
common mental 
pitfalls that can 
sabotage weight loss
Mediterranean 
diet
•• Nutritionally 
balanced
•• Not restrictive
•• Definition of 
Mediterranean diet 
varies
•• 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
•• Indirectly; 
suggestions to use 
smaller plates and eat 
slowly
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.
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4 Nutrition in Clinical Practice XX(X)
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.
Energy Expenditure and Macronutrient 
Composition
There are data to suggest that altering the macronutrient 
composition of the diet provides a metabolic advantage and 
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 
Age
Factors Influencing 
Weight Loss
Behaviors
Body 
composition 
(muscle vs. 
fat) Changing 
food supply
Diet 
composition
Interrelated and Dynamic
Economics
Genetics
Gut
microbiota
Hormones: 
Ghrelin 
Leptin
Insulin
resistance
Insulin
sensitivity
Metabolic rate:
•Physical activity
•Thermic effect 
of foodstuffs
•REE
Religious & 
cultural 
practices
Satiety
Fac
W
lat
FF
n
aa
rr
WW
c
WW ht
ndd 
gh
srs
WW
tootors Ist gaca
WWWeightWW
c gg In
ana
Lo
y
ng ing
m
s
nc
am
incinccF ngcinn
tnInter
ighhth
uenc
Medications
Losst
ctors Ioo
tt
ed andd Dyd nan micnaammicam
Figure 2. Factors influencing weight loss.
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Matarese et al 5
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 
Metabolic Effects
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 
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 effectson 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 
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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 improvedrisk 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
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Matarese et al 7
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
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 
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 
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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 comparedwith 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.
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 
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
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.
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