And the winner is -- Atkins

[Guest guest]

Hi All,

The below is PDF-available and the latest from New Engl J Med on Atkins

versus low-fat diets. And the winner is … Atkins.

[1] review seemed a little like sour grapes in pooh-poohing the dropout

problems.

Not statistically significant, they say in [2], but 9% of those dropping out

of the low-carbohydrate group were women and 24% of the low-carbohydrate

group dropouts were women.

Areas under the glucose curve at 12 months in [3] increased 5.3% for the

low-carbohydrates and 2.4% for the low-fats (not significantly different).

For insulin, the areas under the curve values were both significantly

different 18.4 and 16.5%, respectively.

Insulin sensitivities were significant at 6 but not at 12 months and at 12

months were 4.8 and 5.4%, respectively.

Overall, I thought that the low-carbohydrate dieters lost weight and when

they might have considered the values of various things for subjects losing

the same amount of weight, the values would have mostly or all been not

significantly different.

Cheers, Al.; email: apater@...

[1] Ware, J. H. (2003).

Interpreting Incomplete Data in Studies of Diet and Weight Loss.

N Engl J Med 348: 2136-2137 [Full Text]

The prevalence of obesity among Americans 20 to 74 years of age increased from

15

percent during the period between 1976 and 1980 to 27 percent in 19991 and

continues

to increase, with alarming implications for public health. At any time, about 45

percent of

women and 30 percent of men in this country are actively seeking to lose weight

— in

most cases, to no avail.2 Thus, the public has a keen interest in diets that

might help in the

battle against the bulge.

Although most physicians recommend low-fat diets, low-carbohydrate diets such as

the

Atkins diet have had a substantial following for many years. No diet books have

been so

widely read as Dr. Atkins' New Diet Revolution3 and its companions, of which

more than

10 million copies have been sold. Despite such enthusiasm, few scientific

studies have

evaluated the long-term effects of these diets on weight and lipid levels.

In this issue of the Journal, results from two randomized trials comparing

carbohydrate-restricted diets with fat-restricted diets are reported. et

al.4 enrolled

63 obese men and women in a 12-month study of a low-carbohydrate, high-protein,

high-fat diet. Samaha et al.5 report results of a six-month study of a

carbohydrate-restricted diet in 132 severely obese subjects (with a body-mass

index [the

weight in kilograms divided by the square of the height in meters] of at least

35).

Unfortunately, the reader's ability to draw definitive conclusions about the

relative efficacy

and safety of carbohydrate-restricted and fat-restricted diets in these trials

is limited by the

large percentages of participants who were lost to follow-up. In the study by

and

colleagues, 37 of 63 subjects (59 percent) completed 12 months of follow-up, and

79 of

132 subjects (60 percent) completed 6 months of follow-up in the study by Samaha

et al.

The definitive analysis of randomized clinical trials is the intention-to-treat

analysis, the

analysis that " includes all randomized patients in the groups to which they were

randomly assigned, regardless of . . . the

treatment they actually received, and regardless of subsequent withdrawal from

treatment or deviation from the protocol. " 6 Only

intention-to-treat analyses fully preserve the validity of comparisons between

treatment groups established by randomization.

However, to perform an intention-to-treat analysis, all participants who undergo

randomization must be followed to the

completion of the study. In these two weight-loss trials, the investigators did

not follow participants systematically after they

discontinued the study therapy.

An essential part of good clinical-trials practice is the maximal retention of

study participants, irrespective of their adherence to

the treatment protocol, subject to the constraints of ethical conduct of the

trial and the well-being of participants. With such

large percentages of participants lost to follow-up, any analysis of the data

must differ substantially from an intention-to-treat

analysis and is vulnerable to selection bias arising from differences between

the participants who completed the trial and those

who did not.

One popular method of analyzing incomplete data is known as a " completers "

analysis — that is, an analysis including only the

participants who completed follow-up. In weight-loss trials, such analyses are

almost surely biased. Most participants drop out

because they no longer wish to follow the prescribed diet, and their weight is

likely to rebound. Further potential for bias is

introduced if the attrition rates differ between treatment groups. Another

popular approach is known as the

last-observation-carried-forward method. In this type of analysis, the last

weight observed for each study participant is included

in the analysis of the final follow-up visit. This approach is also almost

surely biased, because the last observed value is an

optimistic estimate of the weight on the date of study completion for those who

dropped out. Moreover,

last-observation-carried-forward analyses artificially inflate the nominal

sample size, resulting in a spurious increase in precision.

Finally, one can use model-based methods for the analysis of incomplete

longitudinal data,7 but these methods assume that the

missing values for participants who are lost to follow-up can be predicted from

the weights of those who remained in the study.

Missing data satisfying this condition are said to be " missing at random. " In

general, none of these methods are defensible in the

typical clinical trial, given that those who drop out are likely to differ from

those who remain in the study, and all of these

methods are particularly suspect in the context of a diet trial.

A less common approach, in which the base-line value is carried forward, may be

of some use in this setting. This type of

analysis can be interpreted as assuming that those who dropped out returned to

their base-line weight. Although this, too, is an

assumption, it is one that has a certain appeal, given the usual recidivism

after weight loss. In the study by et al., the mean

decrease in the weight at six months, according to the analysis in which the

base-line value was carried forward, was 7.0

percent, or about 6.9 kg, in the low-carbohydrate group, and 3.2 percent, or

about 3.1 kg, in the low-fat group (P=0.02). By

12 months, the mean weight losses were 4.4 percent, or about 4.3 kg, in the

carbohydrate-restricted group and 2.5 percent, or

about 2.5 kg, in the fat-restricted group (P=0.26). Similarly, according to the

same type of analysis in the study by Samaha et

al., the mean weight loss at six months was 5.7 kg in the low-carbohydrate group

and 1.8 kg in the low-fat group (P=0.002).

Thus, both studies show significantly more weight loss — a difference of about 4

kg — at 6 months in the low-carbohydrate

group. et al. observed a rebound in weight, so that the difference

between groups was no longer statistically significant at

12 months.

Fortunately, the results based on the various methods of analysis are

consistent, and the studies do provide some insights about

low-carbohydrate diets. In both trials, the participants achieved limited weight

loss, with evidence of rebound over the course of

the trial. The average weight loss was greater in the low-carbohydrate groups

than in the low-fat groups, but the difference was

no longer significant at 12 months in the trial in which follow-up lasted that

long. Finally, the weight loss was small relative to the

amount of excess weight carried by these obese subjects. Thus, these studies,

especially taken together, increase our

knowledge about the effects of low-carbohydrate diets. It is unfortunate,

however, that so much effort must be devoted to

evaluating the implications of missing observations when a seemingly simple

effort to obtain study weights according to the

follow-up protocol would probably have been successful with most participants.

Complete evaluation of enrolled patients,

irrespective of their adherence to study therapy, deserves wider recognition as

an important part of good clinical-trials practice.

References

1.Department of Health and Human Services. The Surgeon General's call to

action to prevent and decrease overweight

and obesity. Rockville, Md.: Office of the Surgeon General, 2001.

2.Serdula MK, Mokdad AH, on DF, Galuska DA, Mendlein JM, Heath GW.

Prevalence of attempting weight

loss and strategies for controlling weight. JAMA

1999;282:1353-1358.[Abstract/Full Text]

3.Atkins RC. Dr. Atkins' new diet revolution. New York: Avon Books, 1992.

4. GD, Wyatt HR, Hill JO, et al. A randomized trial of a

low-carbohydrate diet for obesity. N Engl J Med

2003;348:2082-2090.[Abstract/Full Text]

5.Samaha FF, Iqbal N, Seshadri P, et al. A low-carbohydrate as compared with

a low-fat diet in severe obesity. N Engl J

Med 2003;348:2074-2081.[Abstract/Full Text]

6.Fisher LD, Dixon DO, Herson J, owski RK, Hearron MS, Peace KE.

Intention to treat in clinical trials. In: Peace

KE, ed. Statistical issues in drug research and development. New York:

Marcel Dekker, 1990:331-50.

7.Rubin DB, Little RJA. Statistical analysis with missing data. 2nd ed. New

York: Wiley, 2002.

[2] Samaha FF, Iqbal N, Seshadri P, et al.

A low-carbohydrate as compared with a low-fat diet in severe obesity.

N Engl J Med 2003;348:2074-2081.[Abstract/Full Text]

ABSTRACT

Background The effects of a carbohydrate-restricted diet on weight loss and

risk factors for atherosclerosis have been incompletely assessed.

Methods We randomly assigned 132 severely obese subjects (including 77

blacks and 23 women) with a mean body-mass index of 43 and a high

prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to

a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and

fat-restricted (low-fat) diet.

Results Seventy-nine subjects completed the six-month study. An analysis

including all subjects, with the last observation carried forward for those who

dropped out, showed that subjects on the low-carbohydrate diet lost more

weight than those on the low-fat diet (mean [±SD], –5.8±8.6 kg vs. –1.9±4.2 kg;

P=0.002) and had greater decreases in triglyceride levels (mean, –20±43

percent vs. –4±31 percent; P=0.001), irrespective of the use or nonuse of

hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only

in

subjects without diabetes, also improved more among subjects on the

low-carbohydrate diet (6±9 percent vs. –3±8 percent, P=0.01). The amount of

weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01)

were independent predictors of improvement in triglyceride levels and insulin

sensitivity.

Conclusions Severely obese subjects with a high prevalence of diabetes or the

metabolic syndrome lost more weight during six months on a

carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a

relative improvement in insulin sensitivity and triglyceride levels, even after

adjustment for the amount of weight lost. This finding should be interpreted

with

caution, given the small magnitude of overall and between-group differences in

weight loss in these markedly obese subjects and the short duration of the

study. Future studies evaluating long-term cardiovascular outcomes are

needed before a carbohydrate-restricted diet can be endorsed.

The differences in health benefits between a carbohydrate-restricted diet and a

calorie- and fat-restricted diet are of

considerable public interest. However, there is concern that a

carbohydrate-restricted diet will adversely affect serum lipid

concentrations.1 Previous studies demonstrating that healthy volunteers

following a low-carbohydrate diet can lose weight have

involved few subjects, and few used a comparison group that followed consensus

guidelines for weight loss.2,3 The reported

effects of a carbohydrate-restricted diet on risk factors for atherosclerosis

have varied.2,3,4 We performed a study designed to

test the hypothesis that severely obese subjects with a high prevalence of

diabetes or the metabolic syndrome would have a

greater weight loss, without detrimental effects on risk factors for

atherosclerosis, while on a carbohydrate-restricted

(low-carbohydrate) diet than on a calorie- and fat-restricted (low-fat) diet.

Methods

Subjects

The study was approved by the institutional review board at the Philadelphia

Veterans Affairs Medical Center, and an

approved consent form was signed by each subject. Inclusion criteria were an age

of at least 18 years and a body-mass index

(the weight in kilograms divided by the square of the height in meters) of at

least 35. Exclusion criteria were a serum creatinine

level of more than 1.5 mg per deciliter (132.6 µmol per liter); hepatic disease;

severe, life-limiting medical illness; inability of

diabetic subjects to monitor their own glucose levels; active participation in a

dietary program; or use of weight-loss

medications. During an enrollment period that lasted from May to November 2001,

132 subjects from the Philadelphia

Veterans Affairs Medical Center were randomly assigned to either the

low-carbohydrate diet or the low-fat diet, with use of a

preestablished algorithm generated from a random set of numbers. We used

stratified randomization, with blocking within strata,

to ensure that each group would contain approximately equal numbers of women,

subjects with diabetes, and severely obese

subjects (body-mass index, 40 or higher). The study was not blinded.

Study Design

The two diet groups attended separate two-hour group-teaching sessions each week

for four weeks, followed by monthly

one-hour sessions for five additional months; all sessions were led by experts

in nutritional counseling. Subjects received a

diet-overview handout, instructional nutrition labels, sample menus and recipes,

and a book on counting calories and

carbohydrates.5 No specific exercise program was recommended. The subjects

assigned to the low-carbohydrate diet were

instructed to restrict carbohydrate intake to 30 g per day or less.6 No

instruction on restricting total fat intake was provided.

Vegetables and fruits with high ratios of fiber to carbohydrate were

recommended.6 The subjects assigned to the low-fat diet

received instruction in accordance with the obesity-management guidelines of the

National Heart, Lung, and Blood Institute,7

including caloric restriction sufficient to create a deficit of 500 calories per

day, with 30 percent or less of total calories derived

from fat.

Data Collection

The subjects' weights were measured monthly on a single calibrated scale

(SRScales, SR Instruments). Other data collected at

enrollment and at six months included waist size, self-reported medical history,

blood pressure, and glucose and serum lipid

levels, measured in blood specimens obtained after an overnight fast (Synchron

LX20 Clinical Chemistry System, Beckman

Coulter). Low-density lipoprotein cholesterol levels were calculated according

to the Friedewald formula.8 Serum insulin levels

were measured by radioimmunoassay (Laboratory Corporation of America). Insulin

sensitivity was estimated with use of the

quantitative insulin-sensitivity check index as follows: 1 ÷ [(log fasting

insulin level, in microunits per milliliter) + (log fasting

glucose level, in milligrams per deciliter)]; this index has a good correlation

with the results of glucose-clamp studies in obese

subjects and subjects with diabetes.9 Dietary compliance was estimated by means

of a previously validated10 instrument in

which subjects are interviewed to obtain data on 24-hour recall of dietary

consumption. Data were analyzed with Nutribase

Management software (CyberSoft).

Statistical Analysis

The primary end point was weight loss at six months. Assuming a two-sided type I

error of 5 percent, we estimated that we

would need 100 subjects (50 per group) for the study to have 80 percent power to

demonstrate a mean (±SD) weight loss that

was 5±12 kg greater in the low-carbohydrate group than in the low-fat group.11

Given an anticipated dropout rate of 25

percent, we set the enrollment target at 135 subjects. By six months, 79

subjects remained in the study (36 in the low-fat group

and 43 in the low-carbohydrate group). The primary analysis included all 132

subjects: the 79 subjects who completed the

study, the 29 subjects who dropped out but had six-month data available from

records of routine office visits, and the 24

subjects for whom the weight recorded at the last follow-up visit was carried

forward. Since the 29 subjects whose final weight

was obtained from office records were weighed on a different scale from that

used in the study, we performed a second

analysis that included all subjects, with base-line weights carried forward for

all 53 subjects who dropped out.

For analyses of changes in dietary intake, serum lipid levels, glycemic control,

and insulin sensitivity, we included all subjects,

with base-line values carried forward for subjects who dropped out of the study.

No interim analyses were performed.

For comparison of continuous variables between the two groups, we calculated the

change from base line to six months in each

subject and compared the mean changes in the two diet groups using an unpaired

t-test.12 We assessed the normality of the

distribution of all variables before using the t-test. Triglyceride, insulin,

and glucose levels were skewed and were therefore

log-transformed for analysis. Dichotomous variables were compared by chi-square

analysis.12 Linear regression and two-way

analysis of covariance models were used to correct for potentially confounding

variables and to identify interactions between

variables and diet-group assignment.12 Missing waist sizes were imputed by

linear extrapolation on the basis of height and

weight. All P values were two-sided, and a P value of 0.05 or less was

considered to indicate statistical significance. Analyses

were performed with use of SPSS software (version 10.0).

Results

Base-Line Characteristics

Sixty-eight subjects were randomly assigned to the low-fat diet and 64 to the

low-carbohydrate diet (Figure 1). Subjects in the

two groups were well matched with regard to base-line characteristics (Table 1).

The subjects were severely obese at base line

(Table 1), with a high prevalence of diabetes (39 percent) or the metabolic

syndrome without diabetes (43 percent), as

previously defined.13

Attrition

The cumulative percentage of subjects who dropped out of the study by months 1,

3, and 6 were 38, 44, and 47 percent,

respectively, in the low-fat group and 25, 27, and 33 percent, respectively, in

the low-carbohydrate group. Differences in

attrition between groups were statistically significant by the third month

(P=0.03) but were not significant at six months

(P=0.10). There were no significant differences between the groups in the

characteristics of the subjects who dropped out of

the study (Table 2). Subjects on the low-carbohydrate diet attended more dietary

counseling sessions than did the subjects on

the low-fat diet (mean, 5.7±2.7 vs. 4.3±2.7; P=0.006).

Assessment of Dietary Intake

After six months of dietary counseling, subjects on the low-fat diet reported a

decrease in caloric consumption while their

macronutrient composition was close to the guidelines of the National Heart,

Lung, and Blood Institute (Table 3).7 As

compared with the subjects on the low-fat diet, subjects on the low-carbohydrate

diet reported a nonsignificantly greater

reduction in caloric intake (P=0.33), a significantly greater decrease in the

percentage of calories from carbohydrates

(P<0.001), and a significantly greater increase in the percentage of calories

from protein (P<0.001) and fat (P=0.004).

View this table:

[in this window]

[in a new window]

Table 3. Change from Base Line in the Composition of the Two

Diets at Six Months.

Weight Loss

Subjects on the low-carbohydrate diet lost more weight during the six-month

study than did those on the low-fat diet (mean,

–5.8±8.6 kg vs. –1.9±4.2 kg; 95 percent confidence interval for the difference

in weight loss between groups, –1.6 to –6.3;

P=0.002) (Figure 1). The difference in weight loss between the groups remained

significant after adjustment for base-line

variables alone (age, race or ethnic group, sex, base-line body-mass index,

base-line caloric intake, and the presence or

absence of hypertension, diabetes, active smoking, and sleep apnea) (P=0.002)

and for base-line variables plus the number of

dietary counseling sessions attended (P=0.01).

A second analysis in which we carried forward the base-line weights of subjects

who dropped out of the study (i.e., assumed

no weight loss in these subjects) still demonstrated greater weight loss in the

low-carbohydrate group than in the low-fat group

(mean, –5.7±8.6 kg vs. –1.8±3.9 kg; 95 percent confidence interval for the

difference in weight loss between groups, –1.6 to

–6.2; P=0.002).

As a measure of substantial weight loss, we found that a weight loss of at least

10 percent of the base-line weight occurred in 9

of 64 subjects on the low-carbohydrate diet (14 percent), as compared with 2 of

68 subjects on the low-fat diet (3 percent)

(P=0.02). White subjects lost more weight than black subjects (mean, –13±19 kg

vs. –5±12 kg; P=0.009), regardless of the

diet-group assignment. There were no other significant differences in weight

loss between the groups.

Serum Lipids

During the six-month study, there was a greater decrease in the mean

triglyceride level in the low-carbohydrate group than in

the low-fat group (–20±43 percent vs. –4±31 percent, P=0.001) (Table 4). This

difference remained significant after

adjustment for base-line variables (P<0.001). Subjects on the low-carbohydrate

diet also had a greater mean decrease in

triglyceride levels whether or not they were taking lipid-lowering drugs (–25±38

percent vs. –8±35 percent with lipid-lowering

drugs, P=0.01; and –16±46 percent vs. –1±25 percent without lipid-lowering

drugs; P=0.04). Triglyceride levels may also be

affected by medications taken for diabetes. However, in a separate analysis of

subjects who were not taking either diabetes

medications or lipid-lowering medications (28 on the low-fat diet and 24 on the

low-carbohydrate diet), we still observed a

greater reduction in the mean triglyceride level among subjects on the

low-carbohydrate diet (–20±42 percent vs. 2±28

percent, P=0.001). In a model adjusted for the amount of weight lost and the

base-line variables, assignment to the

low-carbohydrate diet (P=0.01) and the amount of weight lost (P<0.001) were each

independent predictors of a decrease in

the triglyceride level. However, comparison of subjects within weight-loss

strata demonstrated that this finding was limited to

subjects who lost more than 5 percent of their base-line weight.

Black subjects had a smaller decrease in triglyceride levels than did white

subjects (mean, –1±30 percent vs. –21±36 percent),

independent of the diet-group assignment (P=0.002), but not after adjustment for

base-line variables and the amount of weight

lost (P=0.09).

Total cholesterol, high-density lipoprotein cholesterol, and low-density

lipoprotein cholesterol levels did not change significantly

during the six-month study within or between groups (Table 4). During the study,

there were no changes in lipid-lowering

therapy in the low-fat group, whereas two subjects on the low-carbohydrate diet

started taking a statin and one stopped taking

a statin.

Glycemic Control and Insulin Sensitivity

The mean fasting glucose level decreased more in the low-carbohydrate group than

in the low-fat group at six months (–9±19

percent vs. –2±17 percent, P=0.02) (Table 4). This difference remained

significant after adjustment for base-line variables

(P=0.004). However, the greater reduction in serum glucose levels in the

low-carbohydrate group was limited to diabetic

subjects, with no significant change in the levels in nondiabetic subjects on

either diet (Table 4). Assignment to the

low-carbohydrate diet was no longer a significant predictor of a decrease in

glucose levels after adjustment for the amount of

weight lost (P=0.12). There was a trend toward a greater decrease in mean

glycosylated hemoglobin values in diabetic subjects

on the low-carbohydrate diet, as compared with those on the low-fat diet

(P=0.06) (Table 4). By six months, seven subjects in

the low-carbohydrate group had had dose reductions in oral hypoglycemic agents

or insulin. In comparison, one subject in the

low-fat group had a dose reduction in insulin and one subject began oral

therapy.

Insulin sensitivity was measured only in subjects without diabetes. Among these

subjects, those on the low-carbohydrate diet

had a greater increase in insulin sensitivity than those on the low-fat diet

(6±9 percent vs. –3±8 percent, P=0.01). This

difference remained significant after adjustment for base-line variables

(P=0.001). In a model adjusted for the amount of weight

lost and base-line variables, assignment to the low-carbohydrate diet (P=0.01)

and the amount of weight lost (P<0.001) were

each independent predictors of an improvement in insulin sensitivity. Comparison

of subjects within weight-loss strata

demonstrated a uniformly, but nonsignificantly, greater improvement in insulin

sensitivity among those on the low-carbohydrate

diet within each stratum.

Blood Pressure

We did not observe significant overall or between-group changes in blood

pressure. Systolic and diastolic blood pressure

decreased by 2 mm Hg and 1 mm Hg, respectively, in the low-carbohydrate group.

In the low-fat group, both systolic and

diastolic blood pressure decreased by 2 mm Hg (P=0.85 for between-group

differences in the change in systolic blood

pressure and P=0.70 for between-group differences in the change in diastolic

blood pressure). Although many subjects were

receiving antihypertensive therapy at base line (Table 1), none had a change in

this therapy during the study.

Adverse Reactions

One subject on the low-carbohydrate diet was hospitalized with chest pain, which

was ultimately determined to be unrelated to

myocardial ischemia. One subject on the low-carbohydrate diet died from

complications of hyperosmolar coma, which was

thought to be due to poor compliance with drug therapy for diabetes. There was

no clinically significant change in the uric acid

level in either group (Table 4).

Discussion

We found that severely obese subjects with a high prevalence of diabetes and the

metabolic syndrome lost more weight in a

six-month period on a carbohydrate-restricted diet than on a fat- and

calorie-restricted diet. The greater weight loss in the

low-carbohydrate group suggests a greater reduction in overall caloric intake,

rather than a direct effect of macronutrient

composition. However, the explanation for this difference is not clear. Subjects

in this group may have experienced greater

satiety on a diet with liberal proportions of protein and fat. However, other

potential explanations include the simplicity of the

diet and improved compliance related to the novelty of the diet.

Subjects in the low-carbohydrate group had greater decreases in triglyceride

levels than did subjects in the low-fat group;

nondiabetic subjects on the low-carbohydrate diet had greater increases in

insulin sensitivity, and subjects with diabetes on this

diet had a greater improvement in glycemic control. No adverse effects on other

serum lipid levels were observed. Most studies

suggest that lowering triglyceride levels has an overall cardiovascular

benefit.14,15,16 Insulin resistance promotes such

atherosclerotic processes as inflammation,17 decreased size of low-density

lipoprotein particles,18 and endothelial dysfunction.19

Impaired glycemic control in subjects with other features of the metabolic

syndrome markedly increases the risk of coronary

artery disease.20 As expected, we found that the amount of weight lost had a

significant effect on the degree of improvement in

these metabolic factors. However, even after adjustment for the differences in

weight loss between the groups, assignment to

the low-carbohydrate diet predicted greater improvements in triglyceride levels

and insulin sensitivity. Subjects who lost more

than 5 percent of their base-line weight on a carbohydrate-restricted diet had

greater decreases in triglyceride levels than those

who lost a similar amount of weight while following a calorie- and

fat-restricted diet.

There was a consistent trend across weight-loss strata toward a greater increase

in insulin sensitivity in the low-carbohydrate

group, although these changes were small and were not significant within each

stratum. Although greater weight loss could not

entirely account for the greater decrease in triglyceride levels and increase in

insulin sensitivity in the low-carbohydrate group,

we cannot definitively conclude that carbohydrate restriction alone accounted

for this independent effect. Other uncontrolled

variables, such as the types of carbohydrates selected (e.g., the proportion of

complex carbohydrates or the ratio of

carbohydrate to fiber), or other unknown variables may have contributed to this

effect. In addition, more precise measurements

of insulin sensitivity than we used would be needed to confirm this effect of a

carbohydrate-restricted diet.

Many of our subjects were taking lipid-lowering medications and hypoglycemic

agents. Although enrolling these subjects

introduced confounding variables, it allowed the inclusion of subjects with the

obesity-related medical disorders typically

encountered in clinical practice. Analyses from which these subjects were

excluded still revealed greater improvements in insulin

sensitivity and triglyceride levels on a carbohydrate-restricted diet than on a

fat- and calorie-restricted diet.

Our study included a high proportion of black subjects, a group previously

underrepresented in lifestyle-modification studies. As

compared with the white subjects, the black subjects had a smaller overall

weight loss. Future studies should explore whether

greater weight loss in this population can be achieved by more effective

incorporation of culturally sensitive dietary counseling.

The high dropout rate in our study occurred very early and affected our

findings. The very early dropout of these subjects may

indicate that attrition most closely reflected base-line motivation to lose

weight, rather than a response to the dietary intervention

itself.

Taken together, our findings demonstrate that severely obese subjects with a

high prevalence of diabetes and the metabolic

syndrome lost more weight during six months on a carbohydrate-restricted diet

than on a calorie- and fat-restricted diet. The

carbohydrate-restricted diet led to greater improvements in insulin sensitivity

that were independent of weight loss and a greater

reduction in triglyceride levels in subjects who lost more than 5 percent of

their base-line weight. These findings must be

interpreted with caution, however, since the magnitude of the overall weight

loss relative to our subjects' severe obesity was

small, and it is unclear whether these benefits of a carbohydrate-restricted

diet extend beyond six months. Furthermore, the high

dropout rate and the small overall weight loss demonstrate that dietary

adherence was relatively low in both diet groups. This

study proves a principle and does not provide clinical guidance; given the known

benefits of fat restriction, future studies

evaluating long-term cardiovascular outcomes are needed before a

carbohydrate-restricted diet can be endorsed.

References

1.St Jeor ST, BV, Prewitt TE, Bovee V, Bazzarre T, Eckel RH. Dietary

protein and weight reduction: a

statement for healthcare professionals from the Nutrition Committee of the

Council on Nutrition, Physical Activity, and

Metabolism of the American Heart Association. Circulation

2001;104:1869-1874.[Abstract/Full Text]

2.Kennedy ET, Bowman SA, Spence JT, Freedman M, King J. Popular diets:

correlation to health, nutrition, and obesity.

J Am Diet Assoc 2001;101:411-420.[iSI][Medline]

3.Westman EC. A review of very low carbohydrate diets for weight loss. J Clin

Outcomes Manage 1999;6(7):36-40.

4.Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE. Effect of 6-month

adherence to a very low carbohydrate

diet program. Am J Med 2002;113:30-36.[CrossRef][Medline]

5.Natow AB, Heslin J-A. The diabetes carbohydrate & calorie counter. New

York: Simon & Schuster, 1991.

6.Eades MR, Eades MD. Protein power lifeplan. New York: Warner Books,

2000:434.

7.Clinical guidelines on the identification, evaluation, and treatment of

overweight and obesity in adults -- the evidence

report: executive summary. Obes Res 1998;6:Suppl 2:51S-63S. [Erratum, Obes

Res 1998;6:464.][iSI][Medline]

8.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of

low-density lipoprotein cholesterol in

plasma, without use of the preparative ultracentrifuge. Clin Chem

1972;18:499-502.[iSI][Medline]

9.Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check

index: a simple accurate method for assessing

insulin sensitivity in humans. J Clin Endocrinol Metab

2000;85:2402-2410.[Abstract/Full Text]

10.Karvetti RL, Knuts LR. Validity of the 24-hour dietary recall. J Am Diet

Assoc 1985;85:1437-1442.[iSI][Medline]

11.Cohen J. Statistical power analysis for the behavioral sciences. New York:

Academic Press, 1977.

12.Dawson-Saunders B, Trapp RG. Basic and clinical biostatistics. Norwalk,

Conn.: Appleton & Lange, 1990.

13.Expert Panel on Detection, Evaluation, and Treatment of High Blood

Cholesterol in Adults. Executive summary of the

Third Report of the National Cholesterol Education Program (NCEP) Expert

Panel on Detection, Evaluation, and

Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).

JAMA 2001;285:2486-2497.[Full Text]

14.Sacks FM, Tonkin AM, Craven T, et al. Coronary heart disease in patients

with low LDL-cholesterol: benefit of

pravastatin in diabetics and enhanced role for HDL-cholesterol and

triglycerides as risk factors. Circulation

2002;105:1424-1428.[Abstract/Full Text]

15.Rubin HB, Robins SJ, D, et al. Gemfibrozil for the secondary

prevention of coronary heart disease in men with

low levels of high-density lipoprotein cholesterol. N Engl J Med

1999;341:410-418.[Abstract/Full Text]

16.Ginsberg HN. Is hypertriglyceridemia a risk factor for atherosclerotic

cardiovascular disease? A simple question with a

complicated answer. Ann Intern Med 1997;126:912-914.[iSI][Medline]

17.Festa A, D'Agostino R Jr, G, Mykkanen L, RP, Haffner SM.

Chronic subclinical inflammation as part of

the insulin resistance syndrome: the Insulin Resistance Atherosclerosis

Study (IRAS). Circulation

2000;102:42-47.[Abstract/Full Text]

18. BV, Mayer- EJ, Goff D, et al. Relationships between insulin

resistance and lipoproteins in nondiabetic

African Americans, Hispanics, and non-Hispanic whites: the Insulin

Resistance Atherosclerosis Study. Metabolism

1998;47:1174-1179.[iSI][Medline]

19.Stuhlinger MC, Abbasi F, Chu JW, et al. Relationship between insulin

resistance and an endogenous nitric oxide

synthase inhibitor. JAMA 2002;287:1420-1426.[Abstract/Full Text]

20.St-Pierre J, Lemieux I, Vohl MC, et al. Contribution of abdominal obesity

and hypertriglyceridemia to impaired fasting

glucose and coronary artery disease. Am J Cardiol

2002;90:15-18.[iSI][Medline]

[3] GD, Wyatt HR, Hill JO, G. McGuckin, Ed.M., Brill,

B.S., B. Selma Mohammed, M.D., Ph.D., Philippe O. Szapary, M.D., J.

Rader, M.D., S. Edman, D.Sc., and Klein, M.D.

A randomized trial of a low-carbohydrate diet for obesity.

N Engl J Med 2003;348:2082-2090.[Abstract/Full Text]

ABSTRACT

Background Despite the popularity of the low-carbohydrate, high-protein,

high-fat (Atkins) diet, no randomized, controlled trials have evaluated its

efficacy.

Methods We conducted a one-year, multicenter, controlled trial involving 63

obese men and women who were randomly assigned to either a

low-carbohydrate, high-protein, high-fat diet or a low-calorie,

high-carbohydrate, low-fat (conventional) diet. Professional contact was

minimal to replicate the approach used by most dieters.

Results Subjects on the low-carbohydrate diet had lost more weight than

subjects on the conventional diet at 3 months (mean [±SD], –6.8±5.0 vs.

–2.7±3.7 percent of body weight; P=0.001) and 6 months (–7.0±6.5 vs.

–3.2±5.6 percent of body weight, P=0.02), but the difference at 12 months was

not significant (–4.4±6.7 vs. –2.5±6.3 percent of body weight, P=0.26). After

three months, no significant differences were found between the groups in total

or low-density lipoprotein cholesterol concentrations. The increase in

high-density lipoprotein cholesterol concentrations and the decrease in

triglyceride concentrations were greater among subjects on the

low-carbohydrate diet than among those on the conventional diet throughout

most of the study. Both diets significantly decreased diastolic blood pressure

and the insulin response to an oral glucose load.

Conclusions The low-carbohydrate diet produced a greater weight loss

(absolute difference, approximately 4 percent) than did the conventional diet

for

the first six months, but the differences were not significant at one year. The

low-carbohydrate diet was associated with a greater improvement in some risk

factors for coronary heart disease. Adherence was poor and attrition was high

in both groups. Longer and larger studies are required to determine the

long-term safety and efficacy of low-carbohydrate, high-protein, high-fat diets.

At any given time, approximately 45 percent of women and 30 percent of men in

the United States are trying to lose weight.1

Despite these efforts, the prevalence of obesity has doubled in the past 20

years2 and has become a major public health

problem.3 The conventional dietary approach to weight management, recommended by

the leading research and medical

societies,4,5,6,7 is a high-carbohydrate, low-fat, energy-deficit diet.

Low-carbohydrate, high-protein, high-fat diets have become

increasingly popular, and many best-selling diet books have promoted this

approach.8,9 The Atkins diet, originally published in

1973 and again in 1992 and 2002, may be the most popular of these diets. More

than 10 million copies of Atkins's diet book

have been sold,10 and four times as many dieters have read one of the Atkins

books as have read any other diet book.11

Despite its longevity and popularity, no randomized trials evaluating the

efficacy of the Atkins diet have been published.12,13

Data from short-term, uncontrolled studies indicate that the Atkins diet induces

weight losses of 8.3 percent after 8 weeks14

and 10.3 percent after 24 weeks.15

We conducted a one-year, multicenter, randomized, controlled trial to evaluate

the effect of the low-carbohydrate, high-protein,

high-fat Atkins diet on weight loss and risk factors for coronary heart disease

in obese persons. The subjects were randomly

assigned to follow either a low-carbohydrate, high-protein, high-fat Atkins diet

or a high-carbohydrate, low-fat, energy-deficit

conventional diet. Professional contact was minimal, so as to approximate the

approach used by most dieters.

Methods

Subjects

A total of 63 persons (43 women and 20 men) participated in the study (Table 1).

All subjects completed a comprehensive

medical examination and routine blood tests. Potential subjects were excluded if

they had clinically significant illnesses, including

type 2 diabetes; were taking lipid-lowering medications; were pregnant or

lactating; or were taking medications that affect body

weight. All subjects provided written informed consent, and the protocol was

approved by the institutional review boards of the

participating institutions.

Study Design

The subjects were randomly assigned at each site, with use of a random-number

generator, to follow either the

low-carbohydrate diet or the conventional diet. Subjects in both groups were

instructed to take a daily multivitamin supplement

and met with a registered dietitian for 15 to 30 minutes at 3, 6, and 12 months

to review dietary issues.

Low-Carbohydrate Diet

The 33 subjects who were assigned to the low-carbohydrate, high-protein,

high-fat diet met individually with a registered

dietitian before beginning the program to review the central features of the

diet (available as Supplementary Appendix 1 with the

full text of this article at http://www.nejm.org), which involves limiting

carbohydrate intake without restricting consumption of fat

and protein. For the first two weeks, carbohydrate intake is limited to 20 g per

day and is then gradually increased until a stable

and desired weight is achieved. Each subject was given a copy of Dr. Atkins' New

Diet Revolution,10 which details the Atkins

diet program. Subjects were instructed to read the book and follow the diet as

described.

Conventional Diet

The 30 subjects who were assigned to the conventional diet also met with a

registered dietitian before beginning the program to

review the components of a high-carbohydrate, low-fat, low-calorie diet (1200 to

1500 kcal per day for women and 1500 to

1800 kcal per day for men, with approximately 60 percent of calories from

carbohydrate, 25 percent from fat, and 15 percent

from protein) and to receive instructions about calorie counting. Subjects were

given a copy of The LEARN Program for

Weight Management,17 which provides 16 lessons covering various aspects of

weight control. The nutritional information in

the manual was consistent with the dietary recommendations provided by the study

dietitian and with the Department of

Agriculture Food Guide Pyramid.18 Subjects were instructed to read the manual

and follow the program as described.

Outcomes

Body weight was measured with the use of calibrated scales (Detecto 6800,

Cardinal) while the subjects were wearing light

clothing and no shoes at base line and at weeks 2, 4, 8, 12, 16, 20, 26, 34, 42,

and 52. Blood pressure and urinary ketones

were also assessed at base line and at weeks 2, 4, 8, 12, 16, 20, 26, 34, 42,

and 52. Blood samples were obtained after

subjects fasted overnight at base line and at 3, 6, and 12 months to determine

serum lipoprotein concentrations. An oral

glucose-tolerance test was performed at base line and at 3, 6, and 12 months.

After subjects fasted overnight, blood samples

were obtained for the measurement of plasma glucose and insulin concentrations

before and 30, 60, 90, and 120 minutes after

the oral administration of a 75-g glucose load. In addition, insulin

sensitivity, based on fasting plasma glucose and insulin

concentrations, was assessed with the use of quantitative insulin-sensitivity

check index16: 1 ÷ [(log fasting serum insulin level, in

microunits per milliliter) + (log fasting glucose level, in milligrams per

deciliter)].

Analyses of Samples

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, and

triglyceride concentrations were assayed according to

procedures recommended by the Centers for Disease Control and Prevention and the

National Heart, Lung, and Blood

Institute.19 The low-density lipoprotein (LDL) cholesterol concentration was

calculated according to the Friedewald formula20

in all but one subject, who had a triglyceride concentration greater than 400 mg

per deciliter (4.52 mmol per liter). Plasma

insulin was measured by radioimmunoassay, and plasma glucose by a glucose

oxidase autoanalyzer (Yellow Springs

Instruments). The area under the curve (AUC) for the plasma glucose

concentration and for the insulin concentration was

calculated.21 Urinary ketone concentrations were measured with dipsticks

(Ketostix 2880, Bayer) and characterized

dichotomously as negative (0 mg per deciliter) or positive (5 to 100 mg per

deciliter).

Statistical Analysis

Analysis of variance revealed no effects of the research site on weight loss or

attrition at 3, 6, or 12 months, so the data on all

the subjects were analyzed together. A t-test for independent samples was used

to assess differences in base-line variables

between the groups. Two sets of analyses were conducted. The primary analysis

was a repeated-measures analysis of variance

in which the base-line value was carried forward in the case of missing data. In

a secondary analysis, an analysis of covariance

(in which initial weights were covariates) was used to examine changes in weight

from base line to the end of the study, for those

who completed the study, or at the time of the last follow-up visit, for those

who did not complete the study. A chi-square

analysis was performed to determine differences between groups in categorical

variables, and correlations with categorical

variables were assessed with Spearman's rho coefficient. Triglyceride values

were not normally distributed, so the

log-transformed values were analyzed. Results are presented as percent changes

to facilitate clinical interpretation, although all

analyses involved absolute values and were conducted with the use of SPSS

software (version 11.0).22

Results

Weight

In the analysis in which base-line values were carried forward in the case of

missing values, the group on the low-carbohydrate

diet had lost significantly more weight than the group on the conventional diet

at 3 months (P=0.001) and 6 months (P=0.02),

but the difference in weight loss was not statistically significant at 12 months

(P=0.26) (Table 2 and Figure 1A).

Figure 1. Mean (±SE) Percent Change in Weight among

Subjects on the Low-Carbohydrate

Diet and Those on the Conventional (Low-Calorie,

High-Carbohydrate) Diet, According to an

Analysis in Which Base-Line Values Were d Forward

in the Case of Missing Values

(Panel A) or an Analysis That Included Data on Subjects

Who Completed the Study and Data

Obtained at the Time of the Last Follow-up Visit for

Those Who Did Not Complete the Study

(Panel .

In Panel B, the low-carbohydrate group had 28 subjects at

3 months, 24 subjects at 6 months,

and 20 subjects at 12 months and the conventional-diet

group had 21 subjects at 3 months, 18

subjects at 6 months, and 17 subjects at 12 months.

Asterisks indicate a significant difference

(P<0.05) between the groups.

Attrition

A total of 49 subjects completed 3 months of the study (28 on the

low-carbohydrate diet and 21 on the conventional diet), 42

subjects completed 6 months (24 on the low-carbohydrate diet and 18 on the

conventional diet), and 37 subjects completed 12

months (20 on the low-carbohydrate diet and 17 on the conventional diet). The

percentage of subjects who had dropped out of

the study at 3, 6, and 12 months was higher in the group following the

conventional diet (30, 40, and 43 percent, respectively)

than in the group following the low-carbohydrate diet (15, 27, and 39 percent,

respectively), but these differences were not

statistically significant. Overall, 59 percent of subjects completed the study,

and 88 percent of those who completed the

six-month assessment completed the full study. When the analysis included data

on subjects who completed the study and data

obtained at the time of the last follow-up visit for those who did not complete

the study, the pattern of weight loss was similar to

that obtained when the base-line values were carried forward in the case of

missing data. Subjects on the low-carbohydrate diet

lost significantly more weight than the subjects on the conventional diet at 3

months (P=0.002) and 6 months (P=0.03), but the

difference in weight loss was not statistically significant at 12 months

(P=0.27) (Table 3 and Figure 1B).

Urinary Ketones

During the first three months, the percentage of patients who tested positive

for urinary ketones was significantly greater in the

group on the low-carbohydrate diet than in the group on the conventional diet

(Figure 2), but there were no significant

differences between the groups after three months. There was no significant

relation between weight loss and ketosis at any time

during the study.

Blood Pressure

Systolic blood pressure did not change significantly in either group during the

study (Table 2 and Table 3). Diastolic pressure

decreased in both groups, but there were no significant differences between

groups.

Oral Glucose-Tolerance Test

The area under the glucose curve did not change significantly in either group

throughout the study. The area under the insulin

curve decreased in both groups, but there were no significant differences

between groups (Table 2 and Table 3). There were no

significant differences between groups in insulin sensitivity (assessed by the

quantitative insulin-sensitivity check index16)

throughout the study period. Both groups had significant increases in insulin

sensitivity at six months, but the values were not

significantly different from base line at one year (Table 2 and Table 3).

Serum Lipoproteins

The effects of the diets on serum lipoproteins are shown in Table 2 and Table 3

and Figure 3. There were no significant

differences between groups in the total or LDL cholesterol concentration, except

at month 3, when values were significantly

lower in the group on the conventional diet than in the group on the

low-carbohydrate diet. In contrast, the relative increase in

HDL cholesterol concentrations and the relative decrease in triglyceride

concentrations were greater in the group on the

low-carbohydrate diet than in the group on the conventional diet throughout most

of the study. The results of the analyses that

included data on subjects who completed the study and data obtained at the time

of the last follow-up visit for those who did

not complete the study (Table 3) were nearly identical to the analyses in which

base-line values were carried forward in the case

of missing data (Table 2) with respect to blood pressure, insulin sensitivity,

and serum lipoproteins.

Discussion

The results of this multicenter, randomized, controlled trial demonstrate that

the low-carbohydrate, high-protein, high-fat Atkins

diet produces greater weight loss (an absolute difference of approximately 4

percent) than a conventional high-carbohydrate,

low-fat diet for up to six months, but that the differences do not persist at

one year. The magnitude of weight loss at six months

in the low-carbohydrate group approximates that achieved by standard

behavioral23 and pharmacologic24 treatments. These

weight losses are particularly noteworthy because the diet was implemented in a

self-help format and subjects had little contact

with health professionals. The lack of a statistically significant difference

between the groups at one year is most likely due to

greater weight regain in the low-carbohydrate group and the small sample size.

These data suggest that long-term adherence to

the low-carbohydrate Atkins diet may be difficult.

The difference in weight loss between the two groups in the first six months

demonstrates an overall greater energy deficit in the

low-carbohydrate group, despite unrestricted protein and fat intake in this

group and instructions to restrict energy intake in the

conventional-diet group. When the energy content of an energy-deficit diet is

stable, macronutrient composition does not

influence weight loss.25,26,27,28 The mechanism responsible for the decreased

energy intake induced by a low-carbohydrate diet

with unrestricted protein and fat intake is not known but may be related to the

monotony or simplicity of the diet, alterations in

plasma or central satiety factors, or other factors that affect appetite and

dietary adherence. Our data suggest that ketosis was

unlikely to be responsible for the increased weight loss with the

low-carbohydrate diet, since we did not find any relation

between the presence of urinary ketones and weight loss. Furthermore, urinary

ketones were not present in most subjects on

either diet after the first six months.

Although subjects with diabetes were excluded from our study, many — if not most

— of our subjects, because of their

obesity, were probably insulin-resistant with respect to glucose metabolism.29

Treatment with either diet was associated with an

improvement in insulin sensitivity as determined by an oral glucose-tolerance

test; progressively less insulin was secreted to

maintain the same blood glucose concentrations. These data do not demonstrate an

effect of macronutrient composition,

independent of weight loss, on insulin sensitivity in obese subjects without

diabetes. However, the results of these metabolic

studies should be interpreted with caution, given the study's relatively small

sample size and the one-year duration. Additional

studies in which more precise measures of insulin sensitivity are used are

needed to evaluate this issue more carefully.

An important health concern of consuming unrestricted amounts of saturated fat

is the potential to increase the LDL cholesterol

concentration, which is an established risk factor for coronary heart disease.

In fact, at three months, the LDL cholesterol

concentration tended to increase in the subjects on the low-carbohydrate diet

but decreased in the subjects on the conventional

diet, so the difference between groups was significant. Over the long term,

however, the LDL cholesterol concentration among

subjects on the low-carbohydrate diet was similar to base-line values, and the

changes in LDL cholesterol concentrations did

not differ significantly between the groups. These data suggest that the

increased weight loss associated with the

low-carbohydrate diet may offset the adverse effect of saturated fat intake on

serum LDL cholesterol concentrations.

Nonetheless, weight loss with the low-carbohydrate diet was not associated with

the decreases in LDL cholesterol usually

observed with moderate weight loss.4,30

In contrast, the low-carbohydrate diet was associated with greater decreases in

serum triglycerides and greater increases in

HDL cholesterol than was the conventional diet, and the levels of both are also

important risk factors for coronary heart

disease.31,32,33 The magnitude of these changes approximates that obtained with

pharmacologic treatments, such as derivatives

of fibric acid and niacin.31 Although part of this benefit may be due to the

greater weight loss with the low-carbohydrate diet,

the changes are greater than those expected from a moderate weight loss alone.30

Therefore, it is likely that the macronutrient

composition of the diet contributed to the improvement in the HDL

cholesterol–triglyceride axis. High-carbohydrate, low-fat

diets decrease HDL cholesterol concentrations and increase serum triglyceride

concentrations,34,35,36,37 whereas

low-carbohydrate, high-fat diets decrease triglyceride concentrations16,27,37

and increase HDL cholesterol concentrations.15

Moreover, replacing dietary polyunsaturated or monounsaturated fat with

carbohydrate is associated with an increased risk of

coronary heart disease, as predicted by changes in triglyceride and HDL

cholesterol concentrations.38

The overall effect of the low-carbohydrate diet in comparison with a

conventional diet on the risk of coronary heart disease in

our subjects is uncertain. As compared with the conventional diet, the

low-carbohydrate diet was associated with a greater

improvement in some risk factors for coronary heart disease (serum triglycerides

and serum HDL cholesterol), but not others

(blood pressure, insulin sensitivity, and serum LDL cholesterol). Moreover, the

clinical significance of the favorable changes in

the HDL cholesterol–triglyceride axis in the setting of a high fat intake is not

clear. Additional, long-term studies are needed to

determine whether increased serum HDL cholesterol concentrations and decreased

serum triglyceride concentrations have the

same effect on cardiovascular outcomes when one is consuming a diet high in

saturated fat. It is also possible that the large

amount of saturated fats and small amounts of fruits, vegetables, and fiber

consumed during the low-carbohydrate diet can

independently increase the risk of coronary heart disease.39,40 Therefore, at

the present time, there is not enough information to

determine whether the beneficial effects of the Atkins diet outweigh its

potential adverse effects on the risk of coronary heart

disease in obese persons.

Our study has several limitations. The self-help nature of treatment, which is

consistent with the way in which the

low-carbohydrate diet is typically used, probably contributed to the attrition

rate of 41 percent. This high rate of attrition

underscores the difficulty of long-term compliance with either diet, when diet

therapy is given with minimal supervision. More

comprehensive behavioral treatment (e.g., weekly group meetings or

self-monitoring) would probably have decreased attrition,

increased adherence, and made possible a comparison with clinic-based treatments

for obesity.23 Our study was focused on

weight and specific risk factors for coronary heart disease. We did not evaluate

the effect of the low-carbohydrate diet on other

important clinical end points, such as renal function, bone health,

cardiovascular function, and exercise tolerance. Finally, our

findings should not be generalized to overweight subjects or to obese subjects

with serious obesity-related diseases, such as

diabetes and hypercholesterolemia. Additional studies are needed in these

populations to evaluate the safety and efficacy of

low-carbohydrate, high-protein, high-fat diets.

Supported by grants from the National Institutes of Health (RR00036, RR00040,

RR00051, AT1103, DK 37948, DK 56341, DK48520, DK42549,

DK02703, and AT00058).

Dr. reports having received consulting fees from Abbott Laboratories and

HealtheTech and lecture fees from Abbott Laboratories and

Roche Laboratories. Dr. Wyatt reports having received consulting fees from

Ortho-McNeil, USANA, and GlaxoKline and lecture fees from

Roche Laboratories, Abbott Laboratories, Slim-Fast, and Ortho-McNeil. Dr. Hill

reports having received consulting fees from HealtheTech,

& , Procter & Gamble, Coca-Cola, and the International Life

Sciences Institute; lecture fees from Abbott Laboratories, Roche

Laboratories, and Kraft Foods; and grant support from M & M Mars, Procter &

Gamble, and Abbott Laboratories. Dr. Szapary reports having

received lecture fees from AstraZeneca and Kos Pharmaceuticals and grant support

from AstraZeneca. Dr. Klein reports having received

consulting fees from Roche Laboratories and HealtheTech, lecture fees from

Ortho-McNeil, and grants from GlaxoKline and Regeneron.

References

1.Serdula MK, Mokdad AH, on DF, Galuska DA, Mendlein JM, Heath GW.

Prevalence of attempting weight

loss and strategies for controlling weight. JAMA

1999;282:1353-1358.[Abstract/Full Text]

2.Flegal KM, Carroll MD, Ogden CL, CL. Prevalence and trends in

obesity among US adults, 1999-2000.

JAMA 2002;288:1723-1727.[Abstract/Full Text]

3.Department of Health and Human Services. The Surgeon General's call to

action to prevent and decrease overweight

and obesity. Washington, D.C.: Government Printing Office, 2001.

4.Clinical guidelines on the identification, evaluation, and treatment of

overweight and obesity in adults -- the Evidence

Report. Obes Res 1998;6:Suppl 2:51S-209S. [Erratum, Obes Res

1998;6:464.][iSI][Medline]

5. PR, ed. Weighing the options: criteria for evaluating

weight-management programs. Washington, D.C.: National

Academy Press, 1995.

6.Position of the American Dietetic Association: weight management. J Am Diet

Assoc 1997;97:71-74.[iSI][Medline]

7.Krauss RM, Deckelbaum RJ, Ernst N, et al. Dietary guidelines for healthy

American adults: a statement for health

professionals from the National Committee, American Heart Association.

Circulation 1996;94:1795-1800.[Full Text]

8.Steward HL, Bethea MC, s SS, Balart LA. Sugar busters! New York:

Ballantine Publishing, 1995.

9.Eades MR, Eades MD. Protein power. New York: Bantam Books, 1999.

10.Atkins RC. Dr. Atkins' new diet revolution. Rev. ed. New York: Avon Books,

1998.

11.The truth about dieting. Consumer Reports. June 2002:26-32.

12.Freedman MR, King J, Kennedy E. Popular diets: a scientific review. Obes

Res 2001;9:Suppl 1:1S-40S.[iSI][Medline]

13.Blackburn GL, JCC, Morreale S. Physician's guide to popular

low-carbohydrate weight-loss diets. Cleve Clin J

Med 2001;68:761, 765-6, 768.

14.Larosa JC, Fry AG, Muesing R, Rosing DR. Effects of high-protein,

low-carbohydrate dieting on plasma lipoproteins

and body weight. J Am Diet Assoc 1980;77:264-270.[iSI][Medline]

15.Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE. Effect of 6-month

adherence to a very low carbohydrate

diet program. Am J Med 2002;113:30-36.[CrossRef][Medline]

16.Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check

index: a simple, accurate method for assessing

insulin sensitivity in humans. J Clin Endocrinol Metab

2000;85:2402-2410.[Abstract/Full Text]

17.Brownell KD. The LEARN program for weight management 2000. Dallas: American

Health Publishing, 2000.

18.Food guide pyramid. Home and garden bulletin report 252. Washington, D.C.:

Department of Agriculture, 1992.

19.Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of

total serum cholesterol. Clin Chem

1974;20:470-475.[iSI][Medline]

20.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of

low-density lipoprotein in plasma, without

the use of preparative ultracentrifuge. Clin Chem

1972;18:499-502.[iSI][Medline]

21.Potteiger JA, sen DJ, Donnelly JE. A comparison of methods for

analyzing glucose and insulin areas under the

curve following nine months of exercise in overweight adults. Int J Obes

Relat Metab Disord

2002;26:87-89.[CrossRef][Medline]

22.SPSS 11.0 for Windows. Chicago: SPSS, 2000.

23.Wadden TA, GD. Behavioral treatment of obesity. Med Clin North Am

2000;84:441-461.[iSI][Medline]

24.Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002;346:591-602.[Full

Text]

25.Yang M-U, Van Itallie TB. Composition of weight lost during short-term

weight reduction: metabolic responses of obese

subjects to starvation and low-calorie ketogenic and nonketogenic diets. J

Clin Invest 1976;58:722-730.[iSI][Medline]

26.Rabast U, Kasper H, Schonborn J. Comparative studies in obese subjects fed

carbohydrate-restricted and high

carbohydrate 1,000-calorie formula diets. Nutr Metab

1978;22:269-277.[iSI][Medline]

27.Golay A, Allaz AF, Morel Y, de Tonnac N, Tankova S, Reaven GM. Similar

weight loss with low- or

high-carbohydrate diets. Am J Clin Nutr 1996;63:174-178.[Abstract]

28.Golay A, Eigenheer C, Morel Y, Kujawski P, Lehmann T, de Tonnac N.

Weight-loss with low or high carbohydrate

diet? Int J Obes Relat Metab Disord 1996;20:1067-1072.[Medline]

29.Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G.

Insulin resistance and hypersecretion in obesity. J

Clin Invest 1997;100:1166-1173.[Abstract/Full Text]

30.Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids

and lipoprotein: a meta-analysis. Am J Clin

Nutr 1992;56:320-328.[Abstract]

31.Szapary PO, Rader DJ. Pharmacological management of high triglycerides and

low high-density lipoprotein cholesterol.

Curr Opin Pharmacol 2001;1:113-20.

32.Forrester JS. Triglycerides: risk factor or fellow traveler? Curr Opin

Cardiol

2001;16:261-264.[CrossRef][iSI][Medline]

33.Boden WE. High-density lipoprotein cholesterol as an independent risk

factor in cardiovascular disease: assessing the

data from Framingham to the Veterans Affairs High-Density Lipoprotein

Intervention Trial. Am J Cardiol

2000;86:19L-22L.[iSI][Medline]

34.Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids and

lipoproteins: a meta-analysis of 27 trials.

Arterioscler Thromb Vasc Biol 1992;12:911-919.[Abstract]

35.Garg A, Grundy SM, Unger RH. Comparison of effects of high and low

carbohydrate diets on plasma lipoproteins and

insulin sensitivity in patients with mild NIDDM. Diabetes

1992;41:1278-1285.[Abstract]

36.Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle changes for

reversal of coronary heart disease. JAMA

1998;280:2001-2007. [Erratum, JAMA 1999;281:1380.][Abstract/Full Text]

37. SB, Wallin JD, Kane JP, Gerich JE. Effect of diet composition on

metabolic adaptations to hypocaloric nutrition:

comparison of high carbohydrate and high fat isocaloric diets. Am J Clin

Nutr 1977;30:160-170.[Abstract]

38.Hu FB, Stampfer MJ, Manson JE, et al. Dietary fat intake and the risk of

coronary heart disease in women. N Engl J

Med 1997;337:1491-1499.[Abstract/Full Text]

39.Expert Panel on Detection, Evaluation, and Treatment of High Blood

Cholesterol in Adults. Executive summary of the

Third Report of the National Cholesterol Education Program (NCEP) Expert

Panel on Detection, Evaluation, and

Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).

JAMA 2001;285:2486-2497.[Full Text]

40.Schaefer EJ. Lipoproteins, nutrition, and heart disease. Am J Clin Nutr

2002;75:191-212.[Abstract/Full Text]

[Guest guest]

I wonder how the cited drop-out rates compare with dropouts of ANY other

diet. I mean, (aside from the CRONies here), I suspect that diet

dropouts overall are a lot higher than 9/24 percentages.

My understanding is that people flock to Atkins type diet because they

perceive more appetite satisfaction ... vs. health reasons. I would

think that there's a lot of people who would rather maintain a CRON died

if they HAD the strength, wherewithal, etc.

Alan Pater wrote:

> Hi All,

>

> The below is PDF-available and the latest from New Engl J Med on Atkins

> versus low-fat diets. And the winner is & Atkins.

>

> [1] review seemed a little like sour grapes in pooh-poohing the dropout

> problems.

>

> Not statistically significant, they say in [2], but 9% of those

> dropping out

> of the low-carbohydrate group were women and 24% of the low-carbohydrate

> group dropouts were women.

>

>