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 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.

1. 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
550251NCPXXX10.1177/0884533614550251Nutrition in Clinical PracticeMatarese et al
research-article2014
From 1
Division of Gastroenterology, Hepatology and Nutrition,
Department of Internal Medicine, Brody School of Medicine, East
Carolina University, Greenville, North Carolina; 2
Department of
Nutrition Science, East Carolina University, Greenville, North Carolina;
and 3
Department 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 lay
literature and the media on a regular basis. The sheer number of existing diet regimens would suggest that no one diet has been universally
successful at inducing and maintaining weight loss. Many of these dietary programs are based on sound scientific evidence and follow
contemporary principles of weight loss. Others simply eliminate 1 or more of the essential food groups or recommend consumption of 1
type of food at the expense of other foods with little to no supporting evidence. The focus of this review is on weight loss diets, specifically
those with the most supporting scientific evidence and those that are most likely to succeed in achievement and maintenance of desirable
body weight. The effects of weight loss diets on energy expenditure, body weight, body composition, and metabolic parameters will be
evaluated. Ultimately, the best diet is the one the patient will follow and incorporate into his or her daily life for lifelong maintenance of
a healthy body weight. (Nutr Clin Pract.XXXX;xx:xx-xx)
Keywords
body mass index; caloric restriction; weight loss; weight reduction programs; carbohydrate-restricted diet; fat-restricted diet; obesity;
weight loss; glycemic index; Mediterranean diet
at East Carolina University on October 8, 2014ncp.sagepub.comDownloaded from
Adult Weight Loss Diet : Metabolic Effects and OutcomesAdult Weight Loss Diet : Metabolic Effects and Outcomes
Preamble
Keywords
Weight Loss Diets

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

3. 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).
at East Carolina University on October 8, 2014ncp.sagepub.comDownloaded from
Factors Affecting Weight Loss
Calories and Satiety Value

4. 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
•• Healthful behavior
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
a
Adapted 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.
at East Carolina University on October 8, 2014ncp.sagepub.comDownloaded from
Low fiber; may
cause constipation

5. 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 ggIn
ana
Lo
y
nging
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.
at East Carolina University on October 8, 2014ncp.sagepub.comDownloaded from
Composition
Hormones:
Ghrelin
Leptin

6. 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.Acarbohydrate is not simply a uniform organic
compound. Changes in the carbohydrate content of the diet
may be based on the glycemic index or glycemic load, the fiber
content of the specific carbohydrate or complex carbohydrates
vs refined. Yet these are all carbohydrates, which potentially
can be altered in the diet and may have different metabolic
effects. These carbohydrates will vary in their influences on
blood sugar, nutrient density, and hormone levels, all of which
affect tissue metabolism. The same is true for fat. A fat is sim-
ply not one nutrient but rather comprises a collection of mono-
unsaturated, polyunsaturated, saturated fats, and trans fats.
They may include ω-3, ω-6, or ω-9 fatty acids, all of which
have significant effects on inflammation, a major component
of obesity. Protein sources may be derived from plant, marine,
or animal sources. It should also be noted that these macronu-
trients cannot be considered in isolation. As the percentage of
1 of these macronutrients in the diet is reduced, the percentage
of the other 2 macronutrients will increase.
One of the most popular and well-studied alterations in
macronutrient content is carbohydrate. The reason for a carbo-
hydrate restriction is to reduce serum insulin levels and force a
change in substrate metabolism. Low-carbohydrate diets
reduce the dietary contribution to serum glucose, which lowers
insulin levels. Because insulin is an anabolic hormone and a
potent stimulator of lipogenesis and inhibitor of lipolysis, low-
ering insulin levels allows utilization of stored body fat for
energy. Dietary carbohydrate restriction also leads to appetite
suppression and reduced caloric intake. It is also possible that
inefficient protein and fat oxidation leads to extra energy loss.19
This relates back to the second law of thermodynamics. In
many cases, lipolysis is maintained despite excess calories
because glycerol from fat is needed as a gluconeogenic precur-
sor.20
The exact carbohydrate level required to produce this
metabolic shift is thought to be between 20 and 50 g per day in
the initial phases of the diet in comparison with the carbohy-
drate content of the typical Western diet, which often exceeds
300 g per day.
There have been numerous studies that have evaluated the
effects of low-carbohydrate vs low-fat diets in the management
of obesity and its comorbidities. In a systematic review of ran-
domized controlled trials of low-carbohydrate, high-protein
diets vs low-fat diets, the low-carbohydrate, high-protein diets
were more effective at 6 months and are as effective, if not
more, as the low-fat diets in reducing weight and cardiovascu-
lar risk parameters (HDL, triglycerides, systolic blood pres-
sure) risk up to 1 year.21
Hu and colleagues22
performed a
meta-analysis of randomized controlled clinical trials of low-
carbohydrate (≤45%) vs low-fat (≤30%) diets to determine if
differences in the macronutrient content resulted in differences
in weight loss, body composition, and risk factors for diabetes
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Macronutrient Modification and Resulting
Metabolic Effects
Metabolic Syndrome

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

9. 8 Nutrition in Clinical Practice XX(X)
interventions led to improvements in HbA1c, fasting glucose,
fasting insulin, and weight loss. However, the LCKD resulted
in greater improvements in HbA1c (–1.5% vs –0.5%, P = .03),
body weight (–11.1 kg vs –6.9 kg, P = .008), and high-density
lipoprotein cholesterol (+5.6 mg/dL vs 0 mg/dL, P < .001)
compared with the low-glycemic diet. Medications to control
diabetes were reduced or eliminated in 95.2% of the LCKD
group compared with 62% of the low-glycemic index diet
group (P < .01).
One of the largest studies of dietary intervention in type 2
diabetes was conducted by Hussain et al.41
Three hundred
sixty-three overweight and obese participants (102 had type 2
diabetes) were recruited for a 24-week diet intervention trial.
The participants were allowed to choose a low-calorie diet
(LCD) or an LCKD. Body weight, BMI, changes in waist cir-
cumference, blood glucose level, changes in HbA1c, total cho-
lesterol, LDL cholesterol, HDL cholesterol, triglycerides, uric
acid, urea, and creatinine levels were determined before and at
4, 8, 12, 16, 20, and 24 weeks after the administration of the
LCD or LCKD. The initial dose of some antidiabetic medica-
tions was decreased to half, and some were discontinued at the
beginning of the dietary program in the LCKD group. Dietary
counseling and further medication adjustment were done on a
biweekly basis. Both diets had beneficial effects on all of the
parameters examined. However, these changes were more sig-
nificant in subjects who were on the LCKD as compared with
those on the LCD.
Most of the trials evaluating dietary intervention looked at
short-term metabolic outcomes such as actual weight loss,
changes in HbA1c, lipid profiles, and changes in medication
dosages. The Look AHEAD trial evaluated whether modest
weight loss from lifestyle intervention would reduce the rate of
heart attacks and strokes to a lower level than that seen among
similar participants assigned to the diabetes education and sup-
port group.42
All participants received routine medical care
from their own healthcare provider. This landmark study
enrolled >5,000 overweight and obese patients with diabetes,
with a planned follow-up period of up to 13 years. However,
the trial was stopped after 11 years after the trial’s Data and
Safety Monitoring Board reviewed the data and concluded that
there was no difference in the rates of heart attacks and strokes.
It is noteworthy that the overall rates of heart attacks and
strokes among both groups of patients were much lower than
had been anticipated.
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.
References
1. National Institutes of Health, National Heart, Lung and Blood Institute.
NIH Pub No. 00-4084; October 2000.
2. Pories WJ, Dohm LG, Mansfield CJ. Beyond the BMI: the search for bet-
ter guidelines for bariatric surgery. Obesity. 2010;18(5):865-871.
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Summary
Caveats for Macronutrient Modification