PDF link

A Randomized Trial Comparing a Very Low
Carbohydrate Diet and a Calorie-Restricted Low Fat
Diet on Body Weight and Cardiovascular Risk Factors in
Healthy Women

BONNIE J. BREHM, RANDY J. SEELEY, STEPHEN R. DANIELS, AND DAVID A. D’ALESSIO


University of Cincinnati and Children’s Hospital Medical Center, Cincinnati, Ohio 45221

Untested alternative weight loss diets, such as very low carbohydrate
diets, have unsubstantiated efficacy and the potential
to adversely affect cardiovascular risk factors. Therefore,
we designed a randomized, controlled trial to determine
the effects of a very low carbohydrate diet on body composition
and cardiovascular risk factors. Subjects were randomized
to 6 months of either an ad libitum very low carbohydrate
diet or a calorie-restricted diet with 30% of the calories as fat.
Anthropometric and metabolic measures were assessed at
baseline, 3 months, and 6 months. Fifty-three healthy, obese
female volunteers (mean body mass index, 33.6
0.3 kg/m2)
were randomized; 42 (79%) completed the trial. Women on
both diets reduced calorie consumption by comparable
amounts at 3 and 6 months. The very low carbohydrate diet
group lost more weight (8.5
1.0 vs. 3.9
1.0 kg; P < 0.001) and
more body fat (4.8
0.67 vs. 2.0
0.75 kg; P<0.01) than the low
fat diet group. Mean levels of blood pressure, lipids, fasting
glucose, and insulin were within normal ranges in both
groups at baseline. Although all of these parameters improved
over the course of the study, there were no differences observed
between the two diet groups at 3 or 6 months. -
Hydroxybutyrate increased significantly in the very low carbohydrate
group at 3 months (P  0.001). Based on these data,
a very low carbohydrate diet is more effective than a low fat
diet for short-term weight loss and, over 6 months, is not associated
with deleterious effects on important cardiovascular
risk factors in healthy women. (J Clin Endocrinol Metab 88:
1617–1623, 2003)

THE INCIDENCE OF obesity in the United States has
risen continuously over the last several decades, and
the associated medical and economic costs to society are
substantial (1–3). Despite considerable desire on the part of
obese individuals to lose weight (4) and the clear health
benefits of doing so (5), there are currently no proven, effective
approaches for meaningful and long-term weight loss
for most overweight individuals (2). Dietary strategies supported
by the majority of physicians and dietitians, which
emphasize restriction of fat intake, are associated with only
modest weight loss and poor long-term compliance (6, 7).
Given these difficulties and the popular demand for effective
weight loss methods, it is not surprising that a number of diet
plans have been developed outside the medical and nutritional
mainstream that are marketed directly to the public as
weight loss strategies.

The very low carbohydrate, high protein diet, promoted
extensively by Atkins and others, is one of the most popular
of the alternative weight loss approaches (8). The central
rationale of this diet is that severe restriction of dietary carbohydrate
(
10% of daily caloric intake), with its resulting
ketosis, promotes lipid oxidation, satiety, and increased energy
expenditure, factors that should promote negative energy
balance and weight loss (8). However, these purported
responses to very low carbohydrate feeding have not been
established. Furthermore, as studies that severely restrict
carbohydrate intake have all been of short duration (i.e.
6
wk) (9 –16), the clinical benefits of ketogenic diets are
unproven.

Because low carbohydrate diets derive large proportions
of calories from protein and fat, there has been considerable
concern for their potentially detrimental impact on cardiovascular
risk (17). Increased consumption of fat, particularly
saturated fat, has been linked to increased plasma concentrations
of lipids (18), insulin resistance, glucose intolerance
(19, 20), and obesity (21, 22). Therefore, it is possible that
many Americans could actually suffer adverse health effects
by using very low carbohydrate diets in an attempt to lose
weight. To evaluate the effects of a very low carbohydrate
diet on weight loss and cardiovascular risk factors, we randomized
53 healthy obese women to 6 months of a very low
carbohydrate diet or a calorie-restricted, low fat diet conforming
to the guidelines currently recommended by the
American Heart Association and other expert panels (23).

Subjects and Methods

Subjects

Fifty-three obese females were recruited by advertisement and randomized
to the 2 diets based on a prior estimate that 20–25 subjects/
group would be sufficient to demonstrate a 25% difference in weight loss
and a 30% difference in low density lipoprotein (LDL) cholesterol levels
between the 2 regimens. Inclusion criteria were age at least 18 yr, moderate
obesity (body mass index, 30–35), and a stable weight over the
preceding 6 months (no weight loss or gain 10% of their body weight).
Exclusion criteria were the presence of cardiovascular disease, untreated
hypertension, diabetes, hypothyroidism, substance abuse, pregnancy, or
lactation. All subjects gave informed consent for the study, which was
approved by the University of Cincinnati and Cincinnati Children’s
Hospital Medical Center institutional review boards.
Abbreviations: DEXA, Dual energy x-ray absorptiometry; HDL, high
density lipoprotein; LDL, low density lipoprotein.

Assessments

Subject assessments were conducted at the General Clinical Research
Center of Cincinnati Children’s Hospital Medical Center by trained
research nurses. Subjects were screened by medical history and measurements
of height, weight, blood pressure, and fasting glucose, and
each was given an electrocardiogram. Blood pressure measurements
were made by auscultation using an appropriate size cuff with the
subject seated quietly. Individuals meeting the criteria for study participation
were enrolled in the study by the research assistant or the
principal investigator. Subjects gave a sample of fasting blood and had
body fat measured by dual energy x-ray absorptiometry (DEXA) using
a total body scanner (4500A, Hologic, Inc., San Francisco, CA). DEXA
scans were conducted at the body composition core laboratory of the
General Clinical Research Center by trained technicians. Each of these
measures was repeated after 3 and 6 months of diet.

Study diets

The primary objective of the study was to compare the effects of a very
low carbohydrate diet and a calorie-restricted, low fat diet on body
composition and cardiovascular risk factors. Therefore, after each block
of subjects was assessed, the principal investigator used a random number
table to randomly assign those subjects to one of two diets. One
group of dieters was instructed to follow an ad libitum diet with a
maximum intake of 20 g carbohydrate/d (8). It was anticipated that this
diet would induce ketosis. After 2wk of dieting, subjects were permitted
to increase their intake of carbohydrate to 40–60 g/d only if self-testing
of urinary ketones continued to indicate ketosis. The other group of
dieters was instructed on a calorie-restricted, moderately low fat diet
with a recommended macronutrient distribution of 55% carbohydrate,
15% protein, and 30% fat. Calorie prescriptions were based on body size
and calculated using the Harris-Benedict equation (24).
Two registered dietitians delivered a 3-month intervention aimed at
promoting dietary compliance. Group meetings with subjects on the
same diet were held biweekly on the University of Cincinnati campus
and addressed cooking tips, stress management, behavior modification,
and relapse prevention. On alternating weeks, subjects met for individual
counseling sessions during which their assigned dietitian reviewed
their 3-d food records from the previous week, analyzed by Nutritionist
V (First Data Bank, San Bruno, CA), and provided dietary recommendations
and positive reinforcement. Subjects were advised to continue
their baseline level of activity. To control for possible bias, each dietitian
was assigned subjects from each diet group for counseling and alternated
as the meeting facilitator for both groups of dieters. Before each
weekly session, subjects submitted 3-d food records and were weighed
on a single electronic scale (Tanita, Arlington Heights, IL). Blood pressure
was measured, and assessment of urinary ketones was performed
using Ketostix (Bayer Corp., Elkhart, IN). At the end of the 3-month
intervention, subjects were instructed to continue with their weight loss
efforts, but without scheduled contact with the dietitians until the
6-month assessment.

Analyses

Determination of total cholesterol, LDL cholesterol, high density lipoprotein
(HDL) cholesterol, glucose, insulin, leptin,
-hydroxybutyrate,
and triglycerides in fasting plasma were made using conventional
methods (25–27). The results of DEXA and biochemical analyses were
made by personnel blinded to the group assignment of the subjects.

Statistics

Baseline characteristics were compared between the two groups using
t tests. To assess the effects of the diets, two-way repeated measures
ANOVA, with time as the repeated factor, was performed using the
software package SAS (version 8.2, SAS Institute, Inc., Cary, NC). The
level of significance was set at 0.05 for testing the main effects of diet and
time and the interaction effect. If the main effect was significant, the
Bonferroni multiple comparison was implemented to determine the
specific differences. If the interaction was significant, the Bonferroni
adjustment was used to keep the overall level of significance at 0.05.
Differences between groups are indicated only when there is a significant
interaction between diet and time. Body weight, biochemical parameters,
and DEXA measurements were analyzed for the 42 subjects
who completed the study (i.e. those for whom follow-up data were
available). Body weight was also analyzed for the entire randomized
cohort. In this intention to treat analysis, the initial weights for the
subjects who withdrew from the study were used as their follow-up
weights at 3 and 6 months (i.e. an assumption of 0 kg of weight loss). Data
are presented as the mean and se unless designated otherwise.

Results

Subjects

Subjects were recruited through advertisements from May
2000 through January 2001. Fifty-three obese females (13
African-Americans and 40 Caucasians) were enrolled in the
study. Volunteers were enrolled in 3 successive groups of 14,
20, and 19 subjects at 3- to 4-month intervals. Forty-two of the
53 subjects (79%) completed the 6-month study, with 4 dropouts
from the very low carbohydrate diet group and 7 dropouts
from the low fat diet group (Fig. 1). The majority of
subjects discontinuing the study cited difficulty maintaining
the scheduled visits as the primary reason, and follow-up
measurements were obtained for only 1 of the these women.
One subject from each diet group dropped out due to dislike
for their assigned diet. Age and anthropometric characteristics
of those subjects completing the study are included in
Table 1.

Nutrient intake

Subjects randomized to the low fat (n  20) and the very
low carbohydrate (n  22) diet groups consumed similar
amounts of calories at the initiation of the diets (1707  104
and 1608123 kcal respectively) with similar distribution of
macronutrients (Fig. 2). Based on the results of the weekly
food records, subjects complied with their assigned diets.
Although subjects on the carbohydrate-restricted diet were
FIG. 1. Flow chart of subjects in the controlled, randomized weight
loss trial.

not specifically asked to limit caloric intake as were those on
the low fat diet, both groups reported a decrease in caloric
intake of approximately 450 calories compared with baseline.
Although caloric intakes in the two groups were similar, the
proportions of carbohydrate, protein, and fat consumed differed
dramatically. At 3 months, caloric intake in the very
low carbohydrate diet group was distributed as 15% carbohydrate,
28% protein, and 57% fat. In contrast, the low fat diet
group had daily calories distributed as 54% carbohydrate,
18% protein, and 28% fat. At 3 months, the very low carbohydrate
diet group consumed significantly less carbohydrate,
vitamin C, and fiber and significantly more protein,
total fat, saturated fat, monounsaturated fat, polyunsaturated
fat, and cholesterol than the low fat diet group (P
0.01
for all comparisons). At 6 months, the two groups still differed
significantly for most of these measures (Table 2).

Weight and body composition

Body weight and body fat in the low fat and very low
carbohydrate groups were similar at baseline (Table 1). After
the initiation of the diets, both groups had a decrease in body
weight that was more rapid in the earlier weeks of observation
and became less pronounced as the study progressed
(Fig. 3). The women in the very low carbohydrate group lost
an average of 7.6  0.7 kg after 3 months and 8.5  1.0 kg
after 6 months of diet. Women following the low fat diet lost
4.20.8 and 3.91.0 kg at 3 and 6 months, respectively. The
amount of weight lost was significantly greater in the very
low carbohydrate group compared with the low fat group,
whether analyzed as intention to treat with all randomized
subjects in the analysis (P
0.001 at 3 and 6 months) or with
only the subjects who completed the trial (Fig. 3; P
0.001
at 3 and 6 months).

Body composition data for the two groups of women are
shown in Table 3. Both fat mass and fat-free mass decreased
significantly (P
0.001) in the two groups over the course of
the trial. However, similar to body weight, fat mass and lean
body mass decreased significantly more in the very low
carbohydrate group compared with the low fat group at both
3 and 6 months (P
0.01). The reduced fat mass comprised
50–60% of the weight lost in both groups. There were no
changes in bone mineral content over the course of the study.

Cardiovascular risk factors

EKG. There were no electrocardiographic abnormalities in
any of the subjects during the study.
Blood pressure. The blood pressures in the two groups were
within the normal range at the outset of the study and remained
so throughout the study (Table 4). Significant differences
in blood pressure were not found between the
groups during the study.

Plasma lipids. Mean plasma concentrations of total cholesterol,
triglycerides, LDL cholesterol, and HDL cholesterol
were normal in each of the two groups before starting the
diets. A significant interaction (P
0.05) was found for
plasma triglycerides, but this was probably due to a difference
between the groups at baseline. Differences in plasma
lipids between the groups were not detected at the 3- or
6-month assessments (Table 4). Significant time effects (P

0.01) for all of the plasma lipids indicated that the subjects
improved their lipid profiles during the course of the study,
with significant decreases in total cholesterol, LDL cholesterol,
and triglycerides at 3 months and significant increases
in HDL cholesterol at 6 months (Table 4).

Fasting hormones and substrates. Fasting glucose and insulin
did not differ between the two groups at the 3- or 6-month
assessments. However, significant time effects for glucose
(P
0.001) and insulin (P
0.0001) indicate that the glucose
and insulin levels decreased significantly in the women on
both diets over the 6-month study (Table 5). There were no
differences in leptin levels between the two groups (Table 5).
Yet a significant time effect (P
0.0001) shows that plasma
leptin levels decreased significantly in both groups of subjects
at 3 months (Table 5). A significant difference between
the groups was detected for plasma
-hydroxybutyrate, with
this ketone increasing significantly more in the very low
carbohydrate group at 3 months (P  0.0005; Table 5).
Weekly testing of urinary ketones was positive in the majority
of subjects on the very low carbohydrate diet and
negative in those on the low fat diet.

Discussion

The results of this study demonstrate that a very low
carbohydrate diet, taken without a specified restriction of
FIG. 3. Mean body weight of women randomized to very low carbohydrate
and low fat diets over the course of the 6-month trial. The first
time point (wk 1) represents the subjects’ body weights immediately
before randomization. Follow-up for the 2 groups included 17–20
subjects in the low fat group and 19–22 subjects in the very low
carbohydrate group. For subjects missing a follow-up visit, their last
recorded weight is included in the calculation of the group mean.
*, Value different from very low carbohydrate diet group (i.e. significant
interaction of time and diet), P
0.001.

caloric intake, is effective for weight loss over a 6-month
period in healthy, obese women. Compared with the low fat
group, who followed a diet conforming to currently recommended
distributions of macronutrient calories, the very low
carbohydrate group lost significantly more weight, a finding
that was apparent both when the women completing the diet
were considered alone and when the data were analyzed
using intent to treat principles. In addition, despite eating a
high percentage of calories as fat and having relatively high
intakes of saturated fat and cholesterol, the women in the
very low carbohydrate group maintained normal levels of
blood pressure, plasma lipids, glucose, and insulin. These
data suggest that the deleterious effects of diets containing
a high percentage of fat on body weight and cardiac risk
factors are mitigated by restriction of caloric intake and associated
weight loss.

The subjects recruited for this study were healthy adult
women who were moderately obese by current standards. As
such they were representative of many American women
who embark on weight loss efforts each year using the alternative
dietary plans currently marketed in this country.
Although compliance with the diets was assessed primarily
by dietary records, these data are supported by more objective
measures. For example, the average 3-month weight loss
in the low fat diet group (4 kg) is what would be expected
for individuals decreasing their daily caloric consumption by
about 400 kcal (28), approximately the restriction these
women reported making. In addition, there was a significant
correlation between reported changes in caloric intake and
weight loss (r  0.41; P
0.001). Finally, the presence of
measurable ketonemia and ketonuria in the very low carbohydrate
group is consistent with severe carbohydrate restriction
and was not seen in the low fat dieters. Thus, we
believe that the outcomes of this study can be attributed
primarily to differences in the prescribed diets of the two
groups and are applicable to the large number of obese, but
otherwise healthy, American women exploring very low carbohydrate
diets.

One conclusion of previous reports on low carbohydrate
diets was that the increased weight loss was due to the
diuresis that accompanies severe caloric restriction or was
due to decreased body water, presumably accompanying
depletion of stored glycogen (29, 30). However, these studies
were of very short duration, from 1–2 wk in length. Most
diets that have a significant restriction of calories cause a
sodium diuresis that occurs over the first wk or 2 of their use,
and in fact, we noted the most rapid weight loss in both
groups over this period. The low fat diet group lost 1.6 kg in
the first 2 wk, representing 38% of their mean weight loss
during the first 3 months of the study. The very low carbohydrate
group lost 3.0 kg during the first 2 wk, or 39% of their
mean 3-month weight loss. We analyzed body composition
at 3 and 6 months of dieting, well after the expected period
of diuresis. Our analysis of body composition showed that
the weight lost in the very low carbohydrate diet group
consisted of a similar percentage of fat mass as in the low fat
diet group. Thus, we think it is very unlikely that differences
in weight between the two groups at 3 and 6 months are a
result of disproportionate changes in body water in the very
low carbohydrate dieters.

The mechanism of the enhanced weight loss in the very
low carbohydrate diet group relative to the low fat diet group
is not clear. Based on dietary records, the reduction in daily
caloric intake was similar in the two groups. For the greater
weight loss in the very low carbohydrate group to be strictly
a result of decreased caloric consumption, they would have
had to consume approximately 300 fewer calories/d over the
first 3 months relative to the low fat diet group (28). Although
the inaccuracy of dietary records for obese individuals is well
documented (31, 32), it seems unlikely that a systematic
discrepancy of this magnitude occurred between groups of
subjects who were comparably overweight. Therefore, it is
difficult to explain the differences in weight loss between the
two groups primarily as a function of differing caloric intake.
Despite instructions to maintain baseline levels of activity, it
is possible that the women in the very low carbohydrate diet
group exercised more than those in the low fat diet group.
Additionally, it is possible that consuming a very low carbohydrate
diet increases resting or postprandial energy expenditure.
The possibility that differences in the macronutrient
composition of the diet alter energy expenditure is an
interesting question that bears further investigation.
Another unexplained, but important, observation was the
spontaneous restriction of food intake in the very low carbohydrate
diet group to a level equal to that of the control
subjects who were following a prescribed restriction of calories.
This raises the possibility that the very low carbohydrate
diet may have been more satiating. Previous studies
have suggested that, calorie for calorie, protein is more satiating
than either carbohydrate or fat (33, 34), and it may be
that the higher consumption of protein in the very low carbohydrate
diet group played a role in limiting food intake.
Another explanation for restricted food intake in the very
low carbohydrate group is that food choices were probably
greatly limited by the requirements of minimizing carbohydrate
intake, and that dietary adherence per se may have
forced caloric restriction due to practical factors. Although it
has been proposed that ketosis developing from severe carbohydrate
intake contributes to a decrease in appetite (8), this
does not seem likely based on our data. Although the women
following the very low carbohydrate diet developed significant
ketonemia, the elevation of circulating
-hydroxybutyrate
was mild, well below what is seen in other clinical
states of ketosis, such as starvation and diabetic ketoacidosis
(26, 35), and was noted only at 3 months. In addition, there
was no correlation between the level of plasma
-hydroxybutyrate
and weight loss (r  0.29; P  0.43).
This study provides a surprising challenge to prevailing
dietary practice. The current standards for healthy eating
include reducing total fat intake to less than 30% of total
calories and decreasing saturated fat intake to less than 10%.
This recommendation is based on a large body of primarily
epidemiological data and is intended to lower plasma cholesterol
(23), but has been extended by some experts as a
means to decrease the risk of obesity. However, the subjects
on the very low carbohydrate diet experienced significantly
more weight loss than the low fat group and maintained
comparable levels of plasma lipids and other cardiovascular
risk factors while consuming more than 50% of their calories
as fat and 20% as saturated fat. These data indicate that the
role of macronutrient distribution in individuals who are on
weight loss diets needs to be further investigated. In particular,
it seems likely that in the short term, a decrease in total
caloric intake with accompanying weight loss has a greater
impact on nutritionally sensitive parameters such as plasma
lipids than do the macronutrient constituents of the diet.
The results of this study are applicable to healthy persons,
but extension of our findings to subjects with established
cardiovascular risk factors should not be made without further
careful investigation. The mean levels of blood pressure,
glucose, and plasma lipids in our subjects were normal and,
in fact, lower than the average values for American adults
(36). It is possible that very low carbohydrate diets, with high
relative intakes of protein and fat, would have deleterious
effects in subjects with hyperlipidemia, diabetes, or other
metabolic disorders.

Although advocates for very low carbohydrate diets are
likely to embrace the results of this study, several points of
caution need to be emphasized. First, a single study of a
specific dietary regimen cannot provide a full assessment of
safety and efficacy. Despite this study being the longest randomized,
controlled trial of a very low carbohydrate diet
reported, our results are still limited by the 6-month time
frame. Whether the very low carbohydrate diet will produce
sustained weight loss and continued improvement in cardiovascular
risk factors over longer periods of time remains
to be determined; the gradual increase in carbohydrate consumption
in the final 3 months of the study suggests that
some degree of recidivism is likely in persons on this diet. In
addition, increased dietary fat has been linked to certain
types of cancer (37) and may have effects on cardiovascular
health beyond the risk factors assessed in this study. There
was also a low intake of calcium and fiber in the very low
carbohydrate group that would need to be addressed if this
diet were to be used for longer periods. Finally, long-standing
ketosis has been associated with myocardial dysfunction
in children after a ketogenic diet to treat intractable seizures
(38). Despite these concerns, the present results indicate that
there are important, interesting, and poorly understood effects
of severe carbohydrate restriction that warrant further
investigation as we seek effective therapeutic strategies to
manage the epidemic of obesity.

Acknowledgments

We acknowledge the invaluable contributions of Lisa C. Andrews,
M.Ed., R.D.; Jane A. Boback, R.D.; and Suzanne E. Spang, R.D., and
statistical advice from Judy Bean, Ph.D., and Stephen Benoit, Ph.D. We
thank Kay Ellis and Joe Kluener for technical support, and Dr. Evan Stein
and Medical Research Laboratories for determination of lipid
concentrations.

Received September 23, 2002. Accepted January 15, 2003.
Address all correspondence and requests for reprints to: Bonnie
Brehm, Ph.D., University of Cincinnati, P.O. Box 210038, Cincinnati,
Ohio 45221-0038. E-mail: bonnie.brehm~uc.edu.
This work was supported by the American Heart Association, University
of Cincinnati Obesity Research Center, University of Cincinnati
Research Council, Children’s Hospital Medical Center Clinical Research
Center (supported in part by USPHS Grant M01-RR-08084 from the
General Clinical Research Center Program, National Center for Research
Resources, NIH), and NIH Grants DK-54263 and DK-56863.

References

1. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL 1998 Overweight and
obesity in the United States: prevalence and trends, 1960–1994. Int J Obesity
Related Metab Disord 22:39–47
2. Hill JO, Peters JC 1998 Environmental contributions to the obesity epidemic.
Science 280:1371–1374
3. Kuczmarski RJ, Carroll MD, Flegal KM, Troiano RP 1997 Varying body mass
index cutoff points to describe overweight prevalence among U.S. adults:
NHANES III (1988 to 1994). Obesity Res 5:542
4. Serdula MK, Mokdad AH, Williamson DF, Galuska DA, Mendlein JM,
Heath GW 1999 Prevalence of attempting weight loss and strategies for controlling
weight. JAMA 282:1353–1358
5. Mokdad AH, SerdulaMK,DietzWH,BowmanBA, Marks JS, Koplan JP 1999
The spread of the obesity epidemic in the United States, 1991–1998. JAMA
282:1519–1522
6. Toubro S, Astrup A 1997 Randomised comparison of diets for maintaining
obese subjects’ weight after major weight loss: ad lib, low fat, high carbohydrate
diet v fixed energy intake. Br Med J 314:29–34
7. Westerterp KR, Verboeket-van de Venne WP, Westerterp-Plantenga MS,
Velthuis-te Wierik EJ, de Graaf C, Weststrate JA 1996 Dietary fat and body
fat: an intervention study. Int J Obes Relat Metab Disord 20:1022–1026
8. Atkins R 1992 Dr. Atkins new diet revolution. New York: Avon Books
9. Alford BB, Blankenship AC, Hagen RD 1990 The effects of variations in
carbohydrate, protein, and fat content of the diet upon weight loss, blood
values, and nutrient intake of adult obese women. J AmDiet Assoc 90:534–540
10. Baron JA, Schori A, Crow B, Carter R, Mann JI 1986 A randomized controlled
trial of low carbohydrate and low fat/high fiber diets for weight loss. Am J
Public Health 76:1293–1296
11. Golay A, Eigenheer C, Morel Y, Kujawski P, Lehmann T, de Tonnac N 1996
Weight-loss with low or high carbohydrate diet? Int J Obes Relat Metab Disord
20:1067–1072
12. Larosa JC, Fry AG, Muesing R, Rosing DR 1980 Effects of high-protein, low
carbohydrate dieting on plasma lipoproteins and body weight. J Am Diet
Assoc 77:264–270
13. Davie M, Abraham RR, Godsland I, Moore P, WynnV1982 Effect of high and
low carbohydrate diets on nitrogen balance during calorie restriction in obese
subjects. Int J Obes 6:457–462
14. Kasper H, Thiel H, Ehl M 1973 Response of body weight to a low carbohydrate,
high fat diet in normal and obese subjects. Am J Clin Nutr 26:197–204
15. Rickman F, Mitchell N, Dingman J, Dalen JE 1974 Changes in serum cholesterol
during the Stillman diet. JAMA 228:54–58
16. Vazquez JA, Adibi SA 1992 Protein sparing during treatment of obesity:
ketogenic versus nonketogenic very low calorie diet. Metabolism 41:406–414
17. Blackburn GL, Phillips JC, Morreale S 2001 Physician’s guide to popular low
carbohydrate weight-loss diets. Cleve Clin J Med 68:761, 765–766, 768–769,
773–774
18. LawM2000 Dietary fat and adult diseases and the implications for childhood
nutrition: an epidemiologic approach. Am J Clin Nutr 72:1291S–1296S
19. Bennett PH RM, Knowler WC 1997 Epidemiology of diabetes mellitus. In:
Sherwin RS, ed. Diabetes mellitus. Stamford: Appleton and Lange; 373–400
20. Marshall JA, Bessesen DH, Hamman RF 1997 High saturated fat and low
starch and fibre are associated with hyperinsulinaemia in a non-diabetic population:
the San Luis Valley Diabetes Study. Diabetologia 40:430–438
21. Bray GA, Popkin BM 1998 Dietary fat does affect obesity. Am J Clin Nutr
68:1157–1173
22. Samaras K, Kelly PJ, Chiano MN, Arden N, Spector TD, Campbell LV 1998
Genes versus environment. Diabetes Care 21:2069–2076
23. National Institutes of Health NH, Lung, and Blood Institute 1998 Clinical
guidelines on the identification, evaluation, and treatment of overweight and
obesity in adults: the evidence report. Bethesda: NIH
24. Lutz C, Przytulski K 2001 Nutrition and diet therapy. Philadelphia: Davis
25. Morgan DR, Lazaro A 1963 Immunoassay of insulin: two antibody system.
Diabetes 12:115–126
26. Mercer DW, Losos III FJ, Mason L, Kessler Jr GF 1986 Monitoring therapy
with insulin in ketoacidotic patients by quantifying 3-hydroxybutyrate with a
commercial kit. Clin Chem 32:224–225
27. Friedewald WT, Levy RI, Fredrickson DS 1972 Estimation of the concentration
of low density lipoprotein cholesterol in plasma, without use of the
preparative ultracentrifuge. Clin Chem 18:499–502
28. Melanson K, Dwyer J 2002 Popular diets for treatment of overweight and
obesity. In: Wadden TA, Stunkard AJ, eds. Handbook of obesity treatment.
New York: Guilford Press; 249–282
29. Yang MU, Van Itallie TB 1976 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 58:722–730
30. Bortz WM, Wroldson A, Morris P, Issekutz Jr B 1967 Fat, carbohydrate, salt,
and weight loss. Am J Clin Nutr 20:1104–1112
31. Martin LJ, Su W, Jones PJ, Lockwood GA, Tritchler DL, Boyd NF 1996
Comparison of energy intakes determined by food records and doubly labeled
water in women participating in a dietary-intervention trial. Am J Clin Nutr
63:483–490
32. Sawaya AL, Tucker K, Tsay R, Willett W, Saltzman E, Dallal GE, Roberts SB
1996 Evaluation of four methods for determining energy intake in young and
older women: comparison with doubly labeled water measurements of total
energy expenditure. Am J Clin Nutr 63:491–499
33. Barkeling B, Rossner S, Bjorvell H 1990 Effects of a high-protein meal (meat)
and a high-carbohydrate meal (vegetarian) on satiety measured by automated
computerized monitoring of subsequent food intake, motivation to eat and
food preferences. Int J Obes 14:743–751
34. Stubbs RJ, van Wyk MC, Johnstone AM, Harbron CG 1996 Breakfasts high
in protein, fat or carbohydrate: effect on within-day appetite and energy
balance. Eur J Clin Nutr 50:409–417
35. OwenOE, Smalley KJ, D’Alessio DA, MozzoliMA,DawsonEK1998 Protein,
fat and carbohydrate requirements during starvation: anapleurosis and catapleurosis.
Am J Clin Nutr 68:12–34
36. Brown CD, Higgins M, Donato KA, Rohde FC, Garrison R, Obarzanek E,
Ernst ND, HoranM2000 Body mass index and the prevalence of hypertension
and dyslipidemia. Obes Res 8:605–619
37. Lichtenstein AH, Kennedy E, Barrier P, Danford D, Ernst ND, Grundy SM,
Leveille GA, Van Horn L, Williams CL, Booth SL 1998 Dietary fat consumption
and health. Nutr Rev 56:S3–S19
38. Best TH, Franz DN, Gilbert DL, Nelson DP, Epstein MR 2000 Cardiac
complications in pediatric patients on the ketogenic diet. Neurology 54:2328–
2330

PDF link