Weight Loss and Metabolic Benefits With Diets of Varying Fat and Carbohydrate Content: Separating the Wheat From the Chaff

[Guest guest]

More food for thought.

Ralph Giarnella MD

Southington Ct USA

***********************************************************

Weight Loss and Metabolic Benefits With Diets of

Varying Fat and Carbohydrate Content: Separating the

Wheat From the Chaff  CME

Bonnie J. Brehm, PhD, RD    A. D'Alessio, MD   

Nat Clin Pract Endocrinol Metab 4(3):, 2008. © 2008

Nature Publishing Group

Summary and Introduction

Summary

With the rising prevalence of both obesity and

diabetes, the contributing role of diet to the

prevention and treatment of these conditions has

become a major focus of research, clinical practice,

and public policy. There has been intense debate over

which dietary regimens might be most effective for

weight loss, with interest centered on the potential

for specific dietary macronutrients to affect body

composition, metabolism, and overall health. This

Review addresses two regimens with distinct

macronutrient prescriptions that have been widely

touted as being beneficial for weight loss and/or

metabolic profile: diets low in carbohydrate and diets

high in monounsaturated fat. Although data from recent

randomized, controlled trials suggest these popular

diets may be useful for weight control, cardiovascular

health, and glycemic control, longer studies of the

efficacy and safety of varying macronutrient content

are needed to strengthen the evidence base for

nutritional recommendations. Until more support for

specific macronutrient combinations is available,

practitioners can recommend an array of diets with

moderate amounts of macronutrients, tailored to

individual needs and preferences.

Introduction

The concurrent rise in the prevalence of obesity[1]

and diabetes[2] over the past two decades is a major

public health concern. Lifestyle behaviors, such as

nutrient-poor diets and physical inactivity, have been

implicated in the increasing occurrence of both

obesity[3] and diabetes.[4] Large randomized,

controlled trials (RCTs) have demonstrated long-term

weight loss and reduced incidence of diabetes with

lower-fat diets and increased physical activity in

people at high risk.[5,6] Lifestyle modification,

therefore, remains the first clinical approach when

patients present with obesity and attendant metabolic

consequences.

With a pressing need for the prevention and treatment

of obesity and its comorbidities, the therapeutic role

of diet has become a major focus of research, clinical

practice, and public policy. Consequently, there has

been a surge of interest in the potential effects of

diets with varying macronutrient content, with intense

debate about the ideal combination of carbo hydrate,

protein, and fat for effectively managing obesity and

its metabolic consequences such as diabetes and other

cardiovascular risks.

The Acceptable Macronutrient Distribution Ranges

(AMDRs) established by the Institute of Medicine[7]

are widely used as dietary guidelines for healthy

adults, as well as for persons with diabetes.[4] The

AMDRs are as follows: 45-65% of total calories derived

from carbohydrate; 10-35% from protein; 20-35% from

total fat. The overarching goals of these

recommendations include reduction of cardiovascular

risk and achievement of glycemic control, along with

weight management. Specific dietary strategies to

reach these goals must be sensitive to the needs,

values, and preferences of the individual patient.[4]

Similarly to many past and current nutritional

recommendations for health promotion and disease

treatment,[8] the diet recommendations of expert

bodies such as the Institute of Medicine,[7] American

Heart Association,[9] American Diabetes

Association,[4] and European Association for the Study

of Diabetes[10] are based on the clinical expertise

and distillation of available evidence by groups of

leading practitioners. Although long-term dietary

interventions are difficult to implement, there have

been a number of recent randomized, controlled

effectiveness studies that have strengthened the

evidence on which to base clinical nutrition practice.

These studies have provided additional, but not yet

sufficient, evidence for modification of current

nutritional guidelines. Despite a recent flurry of

research, many fundamental questions related to

dietary macronutrients and their effects on energy

balance and metabolism remain unanswered.

The unceasing demand by patients and health-care

providers for effective weight-loss methods has led to

the use of a wide number of unproven strategies. It

is, however, essential for clinicians to be aware of

the latest research findings related to dietary

macronutrients and the sometimes controversial

interpretation and application of these findings. This

Review, therefore, will address two dietary approaches

with a focus on macronutrient composition rather than

energy restriction to promote weight loss and improve

cardiovascular risk: diets low in carbohydrate and

diets high in monounsaturated fat (MUFA).

Diet Debates: A Battle of Macronutrients

Since few nutritional guidelines are based on strong

evidence from rigorous trials, there is considerable

latitude for the manipulation and promotion of

specific macronutrient combinations by health-care

professionals, self-proclaimed experts, and the diet

industry. The purported benefits of popular diets for

improvement of body composition and health are often

attributed to the relative distribution of

macronutrients. These diets cover a wide range of

macronutrients from the Ornish diet, a verylow-fat,

high-carbohydrate diet regimen,[11] to Atkins’

very-low-carbohydrate, high-fat diet,[12] with a

multitude of diets with varying levels of carbohydrate

and fat between these two extremes. Since some of the

alternative diets derive a large proportion of energy

from fat, there has been considerable concern about

potential deleterious effects on cardiovascular

risk.[13]

Although the profusion of unsubstantiated dietary

regimens has been viewed in some quarters as

misleading or even dangerous, one benefit of these

popular diet plans has been to stir debate about the

health effects of macronutrient distribution in the

diet. Recently, several approaches with specific

prescriptions of dietary macronutrients have been

examined in controlled human studies. Two of these

approaches (i.e. restriction of carbohydrate and

enrichment of MUFA) have received considerable

attention. Although some low-carbohydrate studies have

examined modifications in dietary quality (e.g. fiber

content and glycemic index),[14] this article will

focus on the effects of variations in the quantity of

carbohydrate and MUFA in the diet. Although the

published data related to low-carbohydrate and

high-MUFA diets are not sufficient to make overarching

clinical recommendations, an appraisal of the research

in this area provides insights into the effectiveness

of specific dietary constructs to improve important

parameters of health.

Diets Low in Carbohydrate

The popular weight-loss diets that have contributed to

the diet industry’s financial success can be divided

into two camps, namely lowcarbohydrate or low-fat.

Although the medical community traditionally has

supported the moderately low-fat, high-carbohydrate

diet for cardio vascular health,[9] the effectiveness

and safety of weight-loss diets have only recently

been tested in long-term RCTs. In a 2001 scientific

review of popular diets,[13] only four studies of

low-carbohydrate diets were identified within the

previous 20 years, with the longest being 12

weeks.[15-18] The authors, therefore, noted that the

evidence for the effects of low-carbohydrate diets on

weight loss and metabolic outcomes was based on

uncontrolled or nonrandomized trials or observational

studies. They concluded that controlled clinical

trials of both lowcarbo hydrate and low-fat diets are

needed to assess long-term effectiveness and potential

health benefits or detriments.

Several RCTs with at least 6 months of a

lowcarbohydrate diet intervention for weight loss have

been published recently. Although the primary outcome

measure of these studies has been weight loss, the

majority of trials have also examined the diets’

effects on body composition, cardiovascular risk

factors, and glycemic control. The results of these

trials are, therefore, relevant for the vast number of

overweight and obese persons, particularly those who

are also attempting to manage diabetes.

In one of the first of these published studies, the

effects of a low-carbohydrate diet (allowing 20-60 g

of carbohydrate daily) with no energy restriction were

compared with a conventional energy-restricted low-fat

diet, with no more than 30% of energy as total fat. No

recommendations for the specific type of fat were

given.[19] In this trial of obese women, the

low-carbohydrate dieters lost an average of 8.5 kg,

significantly more than the 3.9 kg lost by the low-fat

dieters during the study; the majority of weight loss

in both diet groups occurred during the first 3 months

of dieting. Similarly, fat mass decreased

significantly more in the low-carbohydrate group,

compared with the low-fat group, in proportion to the

amount of weight lost. Several cardio vascular risk

factors (i.e. blood pressure, lipid levels, markers of

systemic inflammation,[20] and fasting glucose and

insulin levels) improved in both diet groups over the

study period.

These findings suggest that a low-carbo hydrate diet

is more effective than a low-fat diet for short-term

weight loss, without detrimental impact on common

cardiovascular risk factors. In addition, participants

assigned to the lowcarbohydrate diet had a spontaneous

restriction of food intake that was comparable to the

energy restriction prescribed for the low-fat diet

group, possibly because of the satiating effect of

dietary protein or the limited variety of food

choices.

Similar responses to low-carbohydrate diets were

reported in 6-month RCTs that included more-severely

obese men and women with a high prevalence of

hyperlipidemia, diabetes, or metabolic

syndrome.[21,22] Again, results showed that the

low-carbohydrate dieters lost significantly more

weight than comparable participants following a

low-fat diet. Additional benefits of the

low-carbohydrate diet suggested by these studies

included greater improvement in levels of

triglycerides[21,22] and HDL-cholesterol.[22] In

addition, diabetic participants in the

low-carbohydrate diet group showed a greater reduction

in serum glucose levels than those in the low-fat diet

group. Insulin sensitivity, measured only in

participants without diabetes, improved more among

those on the low-carbohydrate diet.[21]

and colleagues studied the impact of 1 year of

dieting in obese men and women and found that the

low-carbohydrate diet was more effective for weight

loss after 3 and 6 months than the low-fat diet but,

importantly, not after 12 months;[23] however, the

low-carbohydrate group continued to exhibit greater

improvement in specific cardiovascular risk factors at

12 months (i.e. increased HDL-cholesterol and

decreased triglyceride levels). These findings were

supported by a 1-year follow-up of participants from a

6-month RCT,[24] which additionally showed that, for

diabetic participants, HbA1c levels decreased more in

the low-carbohydrate group. Several other controlled

studies of carbohydrate-restricted diets with

long-term follow-up have shown similar results, with

no differential in weight loss between the diet groups

beyond 6 months,[25-29] but continued improvement in

HDL-cholesterol[26,27,29] and triglyceride levels in

low-carbohydrate groups.[27]

A larger, year-long clinical trial (n = 160) of

overweight and obese adults compared four popular

diets with dissimilar levels of macro nutrients: a

very-low-carbohydrate diet (Atkins diet), a moderately

low-carbohydrate diet (Zone diet), a moderately

low-fat diet (Weight Watchers diet), and a

very-low-fat diet (Ornish diet).[30] After 12 months

of dieting, mean weight loss ranged from 2.1 kg to 3.3

kg for the four diet groups, with no significant

differences between the groups. Increased

self-reported dietary adherence was associated with

greater weight loss and improvement in several

cardiovascular risk factors (i.e. C-reactive protein

and insulin levels and the ratio of total cholesterol

to HDL-cholesterol), regardless of diet type. The

authors, therefore, concluded that the key determinant

of clinical benefits was dietary adherence rather than

the particular macronutrient distribution of the diet.

A recent meta-regression analysis of shortterm studies

of low-carbohydrate dietary interventions (i.e. 4-26

weeks’ duration) found that low-carbohydrate diets are

associated with greater reduction in body mass and

percentage body fat than higher-carbohydrate

diets.[31] A meta-analysis of longer-term RCTs (n =

447) drew the conclusion that low-carbohydrate,

nonenergy-restricted diets are advantageous for weight

loss compared with energy-restricted, low-fat diets

after 6 months, but the difference in weight loss

between diets dissipates after 12 months.[32] Neither

diet showed a clear advantage related to

cardiovascular risk factors. Whereas total cholesterol

and LDL-cholesterol levels decreased more in the

low-fat dieters, HDLcholesterol and triglyceride

levels improved more in the low-carbohydrate dieters.

Without further evidence from long-term trials, it is

uncertain whether the potential of low-carbohydrate

diets for beneficial changes in weight and lipid

profile outweighs the unfavorable changes.[32-34]

One recent study diverges from the apparent consensus

that low-carbohydrate diets have only short-term

weight-loss advantages that dissipate over time. A

well-designed, 1-year trial of overweight and obese

women compared four diets with varying macronutrient

composition (i.e. a conventional moderately low-fat

diet and the Atkins, Zone, and Ornish diets). The

verylow-carbohydrate diet group showed more weight

loss and more-favorable improvement in cardiovascular

risk factors (i.e. blood pressure, HDLcholesterol, and

triglyceride levels), even when controlled for weight

loss.[35] With mean 1-year losses of 1.6 kg to 4.7 kg

among the four diets, and a moderate amount of

variability within the diet groups, one underlying

message of this study is that modest weight loss can

be achieved with assorted diets of varying

macronutrient content.

In conclusion, evidence from recent RCTs provides

reassurance to clinicians that lowcarbohydrate diets

can incur some relative benefits for weight loss and

cardiovascular risk factors for up to 12 months. Given

the potential for increased LDL-cholesterol levels and

individual variability in metabolic response,

clinicians are, however, cautioned to carefully

monitor cardiovascular risk factors, as well as

medications, in patients who are following

low-carbohydrate diets.[33,36]

Importantly, the metabolic effects of dietary regimens

in recent studies of low-carbohydrate and control

diets have been closely tied to weight loss, and it

has not been possible to discern specific effects of

nutrients per se on blood pressure, lipids, or indices

of glucose tolerance. Since the ultimate success of

most diets for weight management is due to consistent

and long-term compliance, a major issue emerging from

the latest research is whether some diets are more

likely to be followed, perhaps because of specific and

severe limitation of food choices or the more

satiating effect of allowed foods.

Diets High in Monounsaturated Fat

If the long-term benefits of varying macro nutrient

distribution are unclear for weight loss, are there

other advantages to systematically varying the fat and

carbohydrate content of the diet? For example, can the

fat content of diets be structured to improve

metabolic parameters? Decreasing the intake of

saturated fat and cholesterol with the goal of

decreasing plasma lipid levels has been an almost

universal prescription for those at risk for

cardiovascular disease or diabetes over the last three

decades. There has, however, been controversy over how

best to replace saturated fat in the diet.

Specifically, it has been argued that diets high in

MUFA may be healthier than diets that substitute

carbohydrate for saturated fat.[37] High-MUFA diets

typical of the Mediterranean region emphasize the

consumption of vegetables, fruits, whole grains,

legumes, nuts, and specific oils (e.g. olive oil,

canola oil), while limiting the intake of saturated

fats from meat, poultry, and dairy products.[38]

Earlier population-based studies, such as the classic

studies of Keys,[39] have suggested an association of

the Mediterranean diet with enhanced longevity and

quality of life. Yet this alleged connection has not

been rigorously tested in well-designed, long-term

clinical trials. Over the past two decades, many

short-term efficacy studies, some in the highly

controlled setting of in-patient metabolic wards, have

compared the effects of high-MUFA diets with highcarbo

hydrate, lower-fat diets. Results from this

work[40-47] suggest that high-MUFA diets may improve

blood pressure, plasma lipid levels, and glycemic

control at least as well as isocaloric

high-carbohydrate diets, without the associated

detrimental changes in triglyceride and HDLcholesterol

concentrations. In addition, the superior

acceptability and palatability of high-MUFA diets may

enhance dietary adherence.[48]

Limitations of these comparative diet studies include

small numbers of participants and short duration. With

no clear definition of the term “high-MUFA diet”, the

prescribed level of MUFA in the study diets varied

considerably, from & #8764;14% to 49% of total energy

intake as MUFA. In the mid-1990s, the American

Diabetes Association published diet recommendations

suggesting that 60-70% of total energy should be

derived from carbohydrate and MUFA.[49] An American

Heart Association Science Advisory[50] concurred that

high-MUFA diets with limited amounts of saturated fat

can be used to manage cardiovascular risk. Yet

practitioners have been reluctant to recommend

high-MUFA diets, perhaps because of the steadfast

belief that high-fat diets will cause increased energy

intake and weight gain when consumed outside of a

controlled setting, even in light of recent studies

showing positive effects of high-fat, low-carbohydrate

diets on weight loss.[32]

In 2003, a 6-month RCT was published, comparing the

effects of a comprehensive Mediterranean Lifestyle

Program that included diet, exercise, stress

management, group support, and smoking cessation to

usual care in 237 postmenopausal women with type 2

diabetes.[51] The intervention group showed greater

decreases in body weight, BMI, and HbA1c levels.

Because of the multifactorial nature of the

intervention, however, study results cannot be

attributed solely to diet effects. Another 6-month RCT

corroborated the weight-loss advantage of a high-MUFA

diet, using a low-calorie, formula-based diet

supplemented with almonds in a group of overweight and

obese adults.[52]

A recent systematic review of studies using

Mediterranean-type diets[53] identified only one

published RCT with the primary objective of testing

the effects of at least 6 months of dieting on

anthropometric parameters.[54] This 18-month

prospective trial (n = 101) compared a

Mediterranean-type diet containing 35% of total energy

from fat (15-20% from MUFA) with a conventional

low-fat diet containing 20% of total energy from fat

(7-8% from MUFA) in overweight and obese adults; both

diets were energycontrolled.[54] Results showed that

participants in both diet groups lost similar amounts

of weight (i.e. about 5% of body weight) at 6 months

and 12 months; however, the Mediterranean-diet group

maintained their lost weight, whereas the low-fat

group regained lost weight at 18 months.

When both active participants and dropouts who were

available for measurements (n = 61) were included in

the analyses, the Mediterraneandiet group showed

greater reduction in body weight, BMI, percentage body

fat, and waist circumference compared with the

low-fat-diet group after 18 months of dieting. The

authors attributed the favorable anthropometric

changes and higher participation rate in the

Mediterranean-diet group (54% versus 20% in the

low-fat group) to the increased palatability of

moderate-fat diets, which enhances dietary adherence

and weight maintenance.

The main objective of other published, longterm RCTs

was to assess the potential benefits of

Mediterranean-type diets on cardiovascular mortality

and risk in populations with prior myocardial

infarctions,[55-57] ischemic heart disease[58] or

identified cardiovascular risk factors,[59,60] with

weight loss only as a secondary endpoint. The Lyon

Diet Heart Study[55-57] and Indo-Mediterranean Heart

Study[59]— long-term, secondary prevention

trials—showed fewer cardiac deaths and nonfatal

myocardial infarctions in the Mediterranean-type-diet

group than in the low-fat-diet group. Some of these

studies documented greater improvement in body weight

and BMI,[59,60] as well as waist circumference,[60]

blood pressure,[59,60] levels of serum

cholesterol,[59,60] triglycerides,[58-60] fasting

blood glucose,[59,60] and insulin resistance[60] in

those individuals assigned to a Mediterranean-style

diet.

To make definitive, scientifically based diet

recommendations, it is essential that controlled

long-term trials be conducted to demonstrate the

health effects of specific percentages of MUFAs and

carbohydrates in the diets of overweight people,

including those with diabetes.

Preliminary results are available from an RCT

comparing the effects of a high-MUFA diet and a

low-fat, high-carbohydrate diet on body weight,

cardiovascular risk factors, and glycemic control over

12 months in 124 overweight people with type 2

diabetes.[61] Energy in the high-MUFA diet was

distributed as approximately 45% carbo hydrate, 15%

protein, and 40% fat (with half being MUFA); energy in

the lowfat diet was distributed as approximately 60%

carbohydrate, 15% protein, and 25% fat. Both diet

prescriptions included comparable caloric restriction

and equal amounts of saturated fat. Both diet groups

showed similar weight loss (about 4 kg) and comparable

improvement in body fat, diastolic blood pressure,

HDLcholesterol, HbA1c, and fasting glucose and insulin

levels over 1 year. These results suggest that

high-MUFA diets can be healthy alternatives to

lower-fat, high-carbohydrate diets without negative

impact on anthropometrics, cardiovascular risk

factors, or glycemic control.

Conclusions

Although research studies indicate that diets with

distinct variations in carbohydrate, protein, and fat

may offer potential health benefits, even the longest

published trials are relatively short. Although 1 year

may seem impossibly long for those conducting or

participating in a clinical trial, it comprises only a

short time in the life of an overweight person.

Despite recent advances in clinical nutrition from

controlled dietary trials of moderate duration, longer

studies of the efficacy and safety of diets with

varying macronutrient content would greatly strengthen

the evidence base for modification of current

recommendations for weight control. The practicality

and cost effectiveness of such research will need

careful consideration. In addition, acute studies that

establish the physiologic mechanisms by which specific

macronutrients contribute to long-term outcomes would

be a valuable complement to extended dietary

interventions.

Current diet recommendations by the major expert

committees and organizations do not encompass extreme

restriction in any macronutrient, but they do allow

for diverse diets with varying amounts of

carbohydrate, protein, and fat. Until more evidence

for specific macronutrient combinations is available,

practitioners can recommend an array of diets with

moderate amounts of macronutrients, tailored to

patients’ needs and preferences. Indeed, long-term

dietary adherence may be improved with individualized

diets that are satiating, palatable, and moderate in

carbohydrate, protein, and fat.

Key Points

• Although diets with distinct variations in

carbohydrate, protein, and fat may offer potential

health benefits, long-term clinical trials are needed

to test the effectiveness and safety of these

diets & #8232;

• Until more evidence for specific macronutrient

combinations is available, practitioners can recommend

an array of diets with moderate amounts of

macronutrients, tailored to the needs and preferences

of patients

Acknowledgments

We would like to acknowledge the valuable

contributions of our collaborators and research team

from our clinical trials: Randy Seeley,

s, Judy Bean, Suzanne Summer, Barbara Lattin,

Jane Boback, s, and Gilchrist. Désirée

Lie, University of California, Irvine, CA, is the

author of and is solely responsible for the content of

the learning objectives, questions and answers of the

Medscapeaccredited continuing medical education

activity associated with this article.

Reprint Address

Bonnie J Brehm, 3110 Vine Street, College of Nursing,

University of Cincinnati, Cincinnati, OH 45221-0038,

USA bonnie.brehm@...

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Authors and Disclosures

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Author

Bonnie J. Brehm, PhD, RD

Professor, College of Nursing, University of

Cincinnati, Cincinnati, Ohio

Disclosure: Bonnie J. Brehm, PhD, RD, has disclosed no

relevant financial relationships.

A. D'Alessio, MD

Professor, College of Medicine, Division of

Endocrinology, Diabetes, and Metabolism, University of

Cincinnati, Cincinnati, Ohio

Disclosure: A. D'Alessio, MD, has disclosed no

relevant financial relationships.

CME Author

Désirée Lie, MD, MSEd

Clinical Professor, Family Medicine, University of

California, Orange; Director, Division of Faculty

Development, UCI Medical Center, Orange, California

Disclosure: Désirée Lie, MD, MSEd, has disclosed no

relevant financial relationships.