Effect of 6-Month Adherence to a Very Low Carbohydrate Diet Program

Effect of 6-Month Adherence to a Very Low
Carbohydrate Diet Program
Eric C. Westman, MD, MHS, William S. Yancy, MD, Joel S. Edman, DSc, Keith F. Tomlin,
Christine E. Perkins, MSW
PURPOSE: To determine the effect of a 6-month very low carbohydrate diet program on body weight and other metabolic
parameters.
SUBJECTS AND METHODS: Fifty-one overweight or obese
healthy volunteers who wanted to lose weight were placed on a
very low carbohydrate diet (⬍25 g/d), with no limit on caloric
intake. They also received nutritional supplementation and recommendations about exercise, and attended group meetings at
a research clinic. The outcomes were body weight, body mass
index, percentage of body fat (estimated by skinfold thickness),
serum chemistry and lipid values, 24-hour urine measurements, and subjective adverse effects.
RESULTS: Forty-one (80%) of the 51 subjects attended visits
through 6 months. In these subjects, the mean (⫾ SD) body
weight decreased 10.3% ⫾ 5.9% (P ⬍0.001) from baseline to 6
months (body weight reduction of 9.0 ⫾ 5.3 kg and body mass
index reduction of 3.2 ⫾ 1.9 kg/m2). The mean percentage of
body weight that was fat decreased 2.9% ⫾ 3.2% from baseline
to 6 months (P ⬍0.001). The mean serum bicarbonate level
decreased 2 ⫾ 2.4 mmol/L (P ⬍0.001) and blood urea nitrogen
level increased 2 ⫾ 4 mg/dL (P ⬍0.001). Serum total cholesterol
level decreased 11 ⫾ 26 mg/dL (P ⫽ 0.006), low-density lipoprotein cholesterol level decreased 10 ⫾ 25 mg/dL (P ⫽
0.01), triglyceride level decreased 56 ⫾ 45 mg/dL (P ⬍0.001),
high-density lipoprotein (HDL) cholesterol level increased 10
⫾ 8 mg/dL (P ⬍0.001), and the cholesterol/HDL cholesterol
ratio decreased 0.9 ⫾ 0.6 units (P ⬍0.001). There were no serious adverse effects, but the possibility of adverse effects in the 10
subjects who did not adhere to the program cannot be eliminated.
CONCLUSION: A very low carbohydrate diet program led to
sustained weight loss during a 6-month period. Further controlled research is warranted. Am J Med. 2002;113:30 –36.
©2002 by Excerpta Medica, Inc.
O
during a 6-week period in 2 studies (7,8). Two previous
studies, involving a total of 30 subjects, have shown that a
very low carbohydrate diet can lead to weight loss during
an 8-week period (9,10).
Because the research regarding very low carbohydrate
diets is limited by small sample sizes and short treatment
duration, the potential risks and benefits of this dietary
approach need further investigation. The purpose of this
study was to assess the effect of a very low carbohydrate
diet program on body weight and other parameters during a 6-month period.
besity has been implicated as the second leading
preventable cause of death in the United States,
and prospective studies suggest that intentional
weight loss leads to a decrease in mortality (1,2). Fewer
than 20% of those attempting to lose weight follow the
mostly widely recommended combination of eating
fewer calories and exercising at least 150 minutes per
week (3). There has recently been a resurgence of diets
promoting low carbohydrate intake, but the scientific evidence supporting the safety and effectiveness of these
diets is limited. Several short-term laboratory studies
have demonstrated that very low carbohydrate diets (carbohydrate intake ⬍25 g/d) can have substantial effects on
metabolism, including weight loss and ketonemia (4).
The magnitude of ketonemia, which is similar to that
observed after fasting but lower than that in diabetic ketoacidosis (5,6), was not associated with adverse effects
From the Division of General Internal Medicine (ECW, WSY, KFT,
CEP), Duke University, Durham, North Carolina; the Ambulatory Care
Service (ECW, WSY), Durham Veterans Affairs Medical Center,
Durham, North Carolina; and the Center for Integrative Medicine
(JSE), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
This study was funded by an unrestricted grant from the Atkins Center for Complementary Medicine, New York, New York.
Requests for reprints should be addressed to Eric C. Westman, MD,
MHS, Division of General Internal Medicine, Suite 200-B Wing, 2200
West Main Street, Durham, North Carolina 27705, or [email protected]
duke.edu
Manuscript submitted April 2, 2001, and accepted in revised form
January 31, 2002.
30
©2002 by Excerpta Medica, Inc.
All rights reserved.
METHODS
Subjects
Generally healthy people who wanted to lose weight were
recruited from the Raleigh/Durham/Chapel Hill areas in
North Carolina. At a screening evaluation, we performed
a medical history and physical examination, and obtained
laboratory tests, urinary ketone measurement, and an
electrocardiogram. Informed consent— using a form
that was approved by the local Institutional Review
Board—was obtained. There were no monetary incentives for participation.
Inclusion/Exclusion Criteria
The inclusion criteria were ages 18 to 65 years, body mass
index from 26 to 33 kg/m2, a desire to lose weight, and no
serious condition requiring medical supervision. Exclusion criteria were use of any prescription medication in
0002-9343/02/$–see front matter
PII S0002-9343(02)01129-4
Very Low Carbohydrate Diet/Westman et al.
the previous 2 months, pregnancy or breast-feeding, any
weight loss diet during the past 6 months, use of prescription diet pills in the last 6 months, and baseline ketonuria.
Intervention
At a baseline visit (the first group meeting following enrollment), instruction in the diet program was provided
and subjects were advised to begin the program on the
following day. A very low carbohydrate diet (carbohydrate intake ⬍25 g/d) was recommended until 40% of a
subject’s self-determined target weight loss was achieved
(11). The daily amount of carbohydrate was then increased to about 50 g. The initial diet consisted of unlimited amounts of meat (i.e., beef, pork, chicken, turkey,
fish, shellfish), unlimited eggs, cheese (4 ounces per day),
salad vegetables (2 cups per day), and low-carbohydrate
vegetables (1 cup per day). Portion sizes of meat and eggs
were not restricted; subjects were instructed to eat until
their hunger was relieved. There was no limit on the
amount of caloric intake. Daily intake of at least six
8-ounce glasses of water was strongly encouraged. Nutritional supplements (multivitamin formula, essential oil
formula, diet formula, chromium picolinate) were provided to subjects to be taken on a daily basis in divided
doses (12) (Appendix). Aerobic exercise was encouraged
at least 3 times per week (at least 20 minutes per session).
No formal exercise program was provided. Group meetings were held every other week for 12 weeks, then every
month for 3 months. At these meetings, a carbohydrate
counter book and several handouts were given to subjects
to reinforce the principles of the dietary program. The
group meetings consisted of dietary counseling, supportive counseling, sharing of food choices, review of urinary
ketone results, and collection of other measurements.
The duration of each visit was approximately 1 hour.
Outcome Measures
Adherence with the diet was measured by self-report,
food records, and urinary ketones. Adherence with exercise was assessed by self-report. A 7-day food record was
completed during the second week of the program, and
24-hour food records were completed at the end of weeks
4 and 16. The total caloric intake, and percentage of dietary intake of protein, carbohydrate, and fat, were calculated by pooling this 9-day sampling (13). Food intake
before the program was not assessed, but based on the
subjects’ height and sex, the mean calculated recommended number of calories was approximately 1905 ⫾
239 kcal/d (14).
Because the intake of fewer than 40 g/d of carbohydrate
results in urinary excretion of ketones, the presence of
ketonuria was used to verify that subjects adhered to the
diet recommendation (4,15). At each return visit, subjects provided a fresh urine specimen for visual analysis
with a standard urine dipstick. Based on the color change
of the dipstick, urinary ketones were assessed on the
ordinal six-point scale: none (0 points), trace: 5 mg/dL
(1 point), small: 5 to 40 mg/dL (2 points), moderate: 40
mg/dL (3 points), large: 80 mg/dL (4 points), large: 160
mg/dL (5 points). The mean level of ketonuria at return
visits throughout the 6 months was categorized into a
3-level ordinal variable for each subject.
Body weight was measured at each visit on the same
scale, at approximately the same time of day (afternoon
or evening), with the subject wearing light clothing but
with shoes removed. Percentage change in body weight
was calculated as: (baseline weight minus follow-up
weight) / (baseline weight). Body mass index was calculated as: (body weight in kg) / (height in m)2. Using standard calipers, the skinfold thickness was measured in 4
body regions (anterior upper arm, posterior upper arm,
abdomen, and subscapular skin) at baseline and at all
visits. The total skinfold thickness was used to estimate
body fat composition (16). At all return visits, blood pressure was measured in the nondominant arm, using an
automated digital cuff after sitting for 3 minutes (Omron
Model HEM-725C, Vernon Hills, Illinois) (17). Two
measurements were taken at each visit and averaged for
the analysis.
Blood tests (sodium, potassium, bicarbonate, chloride,
blood urea nitrogen, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL]
cholesterol, triglycerides, hemoglobin, hematocrit, white
blood count, platelets, thyroid-stimulating hormone)
were administered in the morning after at least 8 hours of
fasting at the screening visit, 8 weeks, 16 weeks, and 24
weeks. Collection of 24-hour urine samples (creatinine,
protein, calcium, uric acid) was on an outpatient basis at
baseline, 8 weeks, 16 weeks, and 24 weeks. A creatinine
sample ⬎1000 mg/d was considered to be adequate. At all
return visits, subjects completed an open-ended adverse
effects questionnaire. At the 20-week and 24-week visits,
subjects completed a checklist of commonly mentioned
adverse effects to estimate frequency of adverse effects.
Statistical Analysis
Paired t tests were used to compare measurements at
baseline and 6 months. Dietary, nutritional supplement,
and exercise adherence were also evaluated using linear
regression as predictors of weight loss (18). A P value of
⬍0.05 was used for statistical significance. The sample
size calculation was based on pilot data suggesting weight
loss during a 6-month period of 13 ⫾ 28 kg. To detect this
amount of weight reduction, with 80% power (2-sided ␣
of 0.05), about 50 subjects were required for the study
(19).
The Atkins Center for Complementary Medicine provided funding for the study, and educational training to
July 2002
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113 31
Very Low Carbohydrate Diet/Westman et al.
Figure 1. Study participant flow.
the research staff. Data collection, analysis, interpretation, and manuscript writing were conducted independently by the research staff.
RESULTS
Two hundred and sixty-eight people were screened by
telephone and a health evaluation, 51 of whom were
enrolled in the study and scheduled for the baseline visit.
Forty-four subjects (86%) attended visits through 8
weeks, whereas 41 (80%) attended visits through 24
weeks (Figure 1). No subject dropped out due to symptomatic adverse effects; 9 were unable to comply with the
diet program, and 1 became pregnant and discontinued
the program. There were no significant differences in demographic characteristics or body weight between those
who remained in the study and those who dropped out
(Table 1).
Fifty subjects (98%) had previously tried to lose weight
using other weight loss programs, 39 (76%) had previously attempted to lose weight at least 2 times, 15 (29%)
had previously used low-carbohydrate, high-protein diets, and 6 (12%) had previously used prescription medication for weight loss. At baseline, 16 subjects (31%)
stated that they exercised 3 or more times per week.
Program Adherence
Of the 41 subjects who continued in the study, 27 (66%)
reported following the dietary recommendations every
day at 2 weeks, 25 (61%) at 12 weeks, and 15 (37%) at 24
weeks. Based on an average of 8 days of food records, the
mean daily caloric intake was 1447 ⫾ 350 kcal (range, 801
to 2322 kcal). The mean daily diet composition was 23 ⫾
32
July 2002
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113
10 g of carbohydrate (range, 8 to 55 g), 115 ⫾ 29 g of
protein (range, 63 to 229 g), and 98 ⫾ 27 g of fat (range,
42 to 168 g). Eighteen (44%) of 41 subjects reported taking the nutritional supplements every day as directed at 2
weeks, 19 (46%) at 12 weeks, and 20 (49%) at 24 weeks.
Twenty-one (51%) reported following the exercise recommendation of exercising 3 or more times per week on
average throughout the study period.
All 41 subjects developed ketonuria. Eight subjects had
a mean level of ketosis greater than “moderate” ketonuria
(ⱖ3), 20 subjects had “moderate” to “trace” ketonuria
(between 1 and 3), and 13 subjects averaged “trace” ketonuria or less (ⱕ1). The level of ketonuria was strongly
correlated with self-reported dietary adherence (P ⫽
0.002), but not with nutritional supplement adherence or
exercise adherence.
Table 1. Baseline Characteristics of the Subjects (n ⫽ 51)
Characteristic
6-Month
Adherers
(n ⫽ 41)
Dropouts
(n ⫽ 10)
P Value
Number (%) or
Mean ⫾ SD
Age (years)
Female sex
White
Body mass index
(kg/m2)
Height (m)
Weight (kg)
43.7 ⫾ 8.9
31 (76)
30 (73)
31.4 ⫾ 2.8
39.8 ⫾ 5.7
7 (70)
5 (50)
32.5 ⫾ 2.4
0.10
0.72
0.16
0.28
1.66 ⫾ 0.89
87.0 ⫾ 11.1
1.64 ⫾ 0.95
90.4 ⫾ 9.3
0.83
0.34
Very Low Carbohydrate Diet/Westman et al.
Figure 2. Effect of a very low-carbohydrate diet and nutritional supplements on body weight (n ⫽ 41). Fat mass estimated from
skinfold thickness measurement. Fat-free mass ⫽ Body weight minus fat mass. Asterisk indicates P ⬍0.001 comparing change from
week 0 to week 24. Error bars represent standard errors of the mean.
Body Weight
Thirty-nine (95%) of the 41 subjects who participated
through 24 weeks lost weight. The overall body weight
change from baseline to 24 weeks was ⫺10.3% ⫾ 5.9% (P
⬍0.001; range, 0% to 20.2%), representing a mean decrease in body mass index of 3.2 ⫾ 1.9 kg/m2 (range, 0 to
6.9 kg/m2) and in body weight of 9.0 ⫾ 5.3 kg (range, 0 to
18.6 kg; Figure 2). Nine subjects (22%) lost from 0% to
5% of body weight, 10 (24%) lost from 5% to 10%, 11
(27%) lost from 10% to 15%, 9 (22%) lost from 15% to
20%, and 2 (5%) lost ⬎20% of body weight. Weight loss
correlated with dietary adherence (P ⬍0.01) and ketonuria (P ⬍0.01), but not with nutritional supplement or
exercise adherence.
Percentage of Body Fat Composition
matocrit, white blood count, or platelet count. One 41year-old woman (height ⫽ 1.65 m, weight ⫽ 93.2 kg at
baseline) had an increase in her thyroid-stimulating hormone level from 7.9 mU/mL at baseline to 13.3 mU/mL at
10 weeks, and was treated with a thyroid supplement by
her physician.
Beneficial effects on serum lipid levels were observed
from baseline to 6 months (Table 3). Twenty-nine (71%)
of the 41 subjects had a reduction in LDL cholesterol
levels from baseline to 24 weeks. In the 12 subjects who
had an increase in LDL cholesterol levels, the mean increase was 18 ⫾ 15 mg/dL (range, 4 to 53 mg/dL). Thirtyseven subjects (90%) had an increase in HDL cholesterol
level from baseline to 24 weeks, but only 1 subject had an
increase in the cholesterol/HDL cholesterol ratio.
Fat mass calculated from skinfold thickness measurements decreased from 36.9 ⫾ 6.2 kg to 30.6 ⫾ 5.7 kg (P
⬍0.001; Figure 2). The nonfat mass decreased from 50.2
⫾ 7.2 kg to 47.0 ⫾ 7.6 kg (P ⬍0.001). The mean calculated percentage of body weight that was fat decreased
2.9% ⫾ 3.2% (from 42.3% to 39.4%) during the study
(P⬍ 0.001).
Urine Tests
Blood Tests
Systolic blood pressure decreased 8 ⫾ 12 mm Hg from
baseline to 24 weeks (P ⬍0.001), whereas diastolic blood
pressure decreased 3 ⫾ 7 mm Hg (P ⬍0.01).
There were statistically significant changes in serum levels
of sodium, chloride, bicarbonate, uric acid, aspartate
aminotransferase, total bilirubin, alkaline phosphatase,
and blood urea nitrogen, and in the blood urea nitrogen/
creatinine ratio (Table 2). There were no significant
changes in levels of creatinine or hemoglobin, or the he-
There was a significant increase in urinary calcium excretion (P ⬍0.001) and uric acid excretion (P ⫽ 0.02) from
baseline to 24 weeks. There was no significant change in
24-hour urine creatinine clearance or protein excretion
during the 24 weeks (Table 3).
Blood Pressure
Adverse Effects
At some point during the 24 weeks, 28 subjects (68%)
reported constipation, 26 (63%) reported bad breath, 21
July 2002
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113 33
Very Low Carbohydrate Diet/Westman et al.
Table 2. Effect of Very Low Carbohydrate Diet Program on Metabolic Indices
Parameter
Baseline
(n ⫽ 41)
Week 8
(n ⫽ 41)
Week 16
(n ⫽ 38)
Week 24
(n ⫽ 41)
Change from Baseline
to Week 24
Mean Difference
(95% Confidence Interval)
P Value
139 ⫾ 1
103 ⫾ 2
25 ⫾ 2
5.0 ⫾ 1
22 ⫾ 9
0.8 ⫾ 0.3
69 ⫾ 15
15 ⫾ 5
0.8 ⫾ 0.2
19 ⫾ 5.5
⫺3 (⫺4 to ⫺2)
⫺1 (⫺2 to 0)
⫺2 (⫺3 to ⫺1)
⫺0.3 (⫺1 to 0)
⫺4 (⫺6 to ⫺2)
0.1 (0 to 0.2)
⫺6 (⫺11 to ⫺1)
2 (1 to 3)
⫺0.1 (⫺0.13 to 0)
4 (3.8 to 4.1)
⬍0.001
0.02
⬍0.001
0.01
0.002
⬍0.001
0.02
⬍0.001
0.06
⬍0.001
Mean ⫾ SD
Sodium (mmol/L)
Chloride (mmol/L)
Bicarbonate (mmol/L)
Uric acid (mg/dL)
Aspartate aminotransferase (U/L)
Total bilirubin (mg/dL)
Alkaline phosphatase (U/L)
Blood urea nitrogen (mg/dL)
Creatinine (mg/dL)
Blood urea nitrogen/creatinine ratio
142 ⫾ 1
104 ⫾ 2
27 ⫾ 2
5.3 ⫾ 1
26 ⫾ 9
0.7 ⫾ 0.3
75 ⫾ 20
13 ⫾ 3
0.9 ⫾ 0.2
15 ⫾ 5
141 ⫾ 2
104 ⫾ 2
26 ⫾ 2
5.2 ⫾ 1
23 ⫾ 8
0.6 ⫾ 0.2
66 ⫾ 14
15 ⫾ 5
0.9 ⫾ 0.2
18 ⫾ 5
(51%) reported headache, 4 (10%) noted hair loss, and 1
woman (3%) reported increased menstrual bleeding.
One subject reported an episode of orthostatic hypotension soon after restarting the diet after a period of nonadherence. This subject continued the diet program with
no further similar episodes. Another subject had moderately severe headaches daily for 3 months, which resolved
without treatment. Thirty-five subjects (85%) reported
more energy, 11 (27%) had decreased heartburn, 30
(73%) had fewer cravings for sweets, 21 (51%) had improved mood, and 8 women (26%) had fewer premenstrual symptoms and less menstrual cramping.
DISCUSSION
In this 6-month uncontrolled study involving motivated,
mildly obese persons, a very low carbohydrate diet pro-
140 ⫾ 2
104 ⫾ 3
24 ⫾ 2
5.2 ⫾ 1
23 ⫾ 9
0.7 ⫾ 0.2
65 ⫾ 14
16 ⫾ 5
0.8 ⫾ 0.2
20 ⫾ 5
gram led to a reduction in body weight that was similar to
the effect of a medication recently approved for the treatment of obesity (20).
Our findings were similar to those of a previous study
using the same dietary approach but without nutritional
supplementation or an exercise recommendation (9). In
that study, 24 mildly overweight persons were instructed
to follow a very low carbohydrate diet during an 8-week
period. On average, subjects lost 7.7 kg of body weight,
and the serum uric acid level increased from 5.9 to 7.7
mg/dL (P ⬍0.01). In contrast, we observed a reduction in
serum uric acid levels, but found a statistically significant
increase in urinary uric acid excretion. The self-reported
food intake was similar in the 2 studies; in the previous
study, subjects ingested a mean of 1461 kcal, 107 g of
protein, 108 g of fat, and 6 g of carbohydrate per day (9).
We estimate that in our study, 66% of the weight lost was
Table 3. Effect of Very Low Carbohydrate Diet Program on Serum Lipid Level and 24-Hour Urinary Excretion
Parameter
Baseline
(n ⫽ 41)
Week 8
(n ⫽ 41)
Week 16
(n ⫽ 38)
Week 24
(n ⫽ 41)
Change from Baseline
to Week 24
Mean Difference
(95% Confidence Interval) P Value
Mean ⫾ SD
Total cholesterol (mg/dL)
LDL cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Non-HDL cholesterol (mg/dL)
Triglycerides (mg/dL)
Total cholesterol/HDL cholesterol ratio
Triglycerides/HDL cholesterol ratio
Urinary creatinine clearance (mL/min)*
Urinary calcium (mg/24 h)*
Urinary uric acid (mg/24 h)*
Urinary protein (mg/24 h)*
214 ⫾ 35
136 ⫾ 32
52 ⫾ 14
162 ⫾ 37
130 ⫾ 62
4.3 ⫾ 1.3
2.8 ⫾ 2.0
124 ⫾ 30
162 ⫾ 109
540 ⫾ 202
119 ⫾ 54
201 ⫾ 37
136 ⫾ 36
49 ⫾ 11
152 ⫾ 39
82 ⫾ 32
4.3 ⫾ 1.2
1.8 ⫾ 1.0
126 ⫾ 33
289 ⫾ 152
630 ⫾ 337
145 ⫾ 85
201 ⫾ 42
128 ⫾ 39
58 ⫾ 13
143 ⫾ 42
75 ⫾ 30
3.6 ⫾ 1.0
1.4 ⫾ 0.7
128 ⫾ 38
306 ⫾ 159
542 ⫾ 240
130 ⫾ 53
203 ⫾ 36
126 ⫾ 34
62 ⫾ 15
141 ⫾ 37
74 ⫾ 33
3.4 ⫾ 0.9
1.3 ⫾ 0.9
129 ⫾ 26
248 ⫾ 120
635 ⫾ 155
134 ⫾ 50
⫺11 (⫺19 to ⫺3)
⫺10 (⫺18 to ⫺2)
10 (8 to 12)
⫺21 (⫺29 to ⫺13)
⫺56 (⫺70 to ⫺42)
⫺0.9 (⫺1.1 to ⫺0.7)
⫺1.5 (⫺1.9 to ⫺1.1)
5 (⫺4 to 14)
86 (44 to 128)
95 (20 to 170)
15 (⫺10 to 40)
* Urinary changes are assessed using a paired t test comparing baseline to week 24; n ⫽ 24 at each time point.
HDL ⫽ high-density lipoprotein; LDL ⫽ low-density lipoprotein; non-HDL cholesterol ⫽ total cholesterol minus HDL cholesterol.
34
July 2002
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113
0.006
0.01
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
0.33
⬍0.001
0.02
0.25
Very Low Carbohydrate Diet/Westman et al.
fat mass, similar to other studies involving dietary interventions for weight loss (21).
Most subjects had a favorable change in their lipid profile. These findings are in contrast with 2 small studies of
similar dietary interventions, in which one found an average increase in serum cholesterol level of 33 mg/dL after
1 week in 12 healthy volunteers, and the other reported a
significant increase in LDL cholesterol level of 23 mg/dL
(P ⬍0.01) (9,22). In our study, 1 subject had an increase
in LDL cholesterol level from 123 mg/dL to 225 mg/dL,
which then was reduced to 176 mg/dL with the addition
of a cholesterol-lowering nutritional supplement formula while continuing the diet. In studies using other
approaches for weight loss, this magnitude of weight loss
has typically been associated with a reduction in total
cholesterol levels of 13%, reduction in LDL cholesterol
levels of 11%, reduction of triglyceride levels of 32%, and
elevation in HDL cholesterol levels of 3% (23).
We observed that levels of serum bicarbonate decreased and blood urea nitrogen increased during a very
low carbohydrate diet program. Even though the serum
bicarbonate levels in this study were still in the normal
range, the long-term effects of a decreased bicarbonate
level (mild metabolic acidosis) are not known. There was
also an increase in urinary excretion of calcium and uric
acid, possibly resulting from ketosis, proteinuria, or
weight loss (24,25). Because dietary intake at baseline was
not recorded, more precise measurement of calcium balance is needed to interpret these changes.
Information about the potential adverse effects of carbohydrate restriction comes from 2 other diets. The “ketogenic diet” is a specific treatment for epilepsy that consists of a high-fat, low-carbohydrate, low-protein diet to
induce the formation of ketone bodies (26). Adverse effects of this diet in children have included calcium oxalate
and urate kidney stones (from 0.5% to 5.0% incidence in
1 year), vomiting, amenorrhea, hypercholesterolemia,
and water-soluble vitamin deficiencies (27,28). The “protein-sparing modified fast” is a specific type of very lowcalorie diet, with extreme limitation of carbohydrate and
calories (⬍800 kcal/d) (29,30). Because the very low-carbohydrate diet that we used provided more than 800
kcal/d, yet also led to ketonemia, it is probably most appropriately labeled as a “ketogenic low-calorie diet.”
Limitations of this study include the uncontrolled design, self-report of several variables, and the use of skinfold calipers to estimate fat mass (31). Because only
healthy volunteers were studied, caution should be used
when generalizing these results to patients with medical
illnesses. Although the dropout rate and adherence to this
diet program are similar to that seen in other weight loss
studies, the possibility of adverse effects in those who did
not adhere to the program cannot be eliminated (32).
In summary, this study describes the metabolic
changes associated with a very low carbohydrate diet pro-
gram when used for weight loss during a 6-month period.
Further controlled research is needed to determine estimate the risks and benefits of this diet in healthy persons
and in patients with other medical conditions.
ACKNOWLEDGMENT
Special thanks to Jacqueline Eberstein, Bill Bryson, and Lamont
Wade.
REFERENCES
1. Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA. 1999;282:1530 –1538.
2. Serdula MK, Mokdad AH, Williamson DF, et al. Prevalence of attempting weight loss and strategies for controlling weight. JAMA.
1999;282:1353–1358.
3. Williamson DF, Pamuk E, Thun M, et al. Prospective study of intentional weight loss and mortality in never-smoking overweight
U.S. white women aged 40 – 64 years. Am J Epidemiol. 1995;141:
1128 –1141.
4. Westman EC. A review of very low carbohydrate diets. J Clin Outcomes Manage. 1999;6:36 –40.
5. Phinney SD, Bistrian BR, Wolfe RR, Blackburn GL. The human
metabolic response to chronic ketosis without caloric restriction:
physical and biochemical adaptation. Metabolism. 1983;32:757–
768.
6. Atkinson RL, Kaiser DL. Effects of calorie restriction and weight
loss on glucose and insulin levels in obese humans. J Am Coll Nutr.
1985;4:411–419.
7. Langfort J, Pilis W, Zarzeczny R, et al. Effect of low-carbohydrateketogenic diet on metabolic and hormonal responses to graded
exercise in men. J Phys Pharm. 1996;47:361–371.
8. Hall SHE, Wastney ME, Bolton TM, et al. Ketone body kinetics in
humans: the effects of insulin-dependent diabetes, obesity, and
starvation. J Lipid Res. 1984;25:1184 –1194.
9. 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.
10. Willi SM, Oexmann MJ, Wright NM, et al. The effects of a highprotein, low-fat, ketogenic diet on adolescents with morbid obesity:
body composition, blood chemistries, and sleep abnormalities. Pediatrics. 1998;101:61–67.
11. Atkins RC. Dr. Atkins’ New Diet Revolution. New York: Simon &
Schuster; 1998.
12. Hathcock JN. Vitamins and minerals: safety and efficacy. Am J Clin
Nutr. 1997;66:427–437.
13. Nutritionist Five [software]. Version 1.6. San Bruno, CA: First
Databank; 2000.
14. Bray GA. The syndromes of obesity: an endocrine approach. In:
Degroot LJ, ed. Endocrinology. 3rd ed. Philadelphia: W.B. Saunders;
1995:2648.
15. Free HM, Smeby RR, Cook MH, Free AH. A comparative study of
qualitative tests for ketones in urine and serum. Clin Chem. 1958;
4:323–330.
16. Durnin JVGA, Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on
481 men and women aged from 16 to 72 years. Br J Nutr. 1974;32:
77–97.
17. Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Rockville,
MD: National Institutes of Health, National Heart, Lung, and
Blood Institute; 1997. NIH publication 98-4080.
July 2002
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113 35
Very Low Carbohydrate Diet/Westman et al.
18. PC SAS for Windows [software]. Version 6.08. Cary, NC: SAS Institute.
19. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd
ed. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988:54.
20. Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces
dose-related weight loss. Obes Res. 1999;7:189 –198.
21. Evans EM, Saunders MJ, Spano MA, et al. Body-composition
changes with diet and exercise in obese women: a comparison of
estimates from clinical methods and a 4-component model. Am J
Clin Nutr. 1999;70:5–12.
22. Rickman F, Mitchell N, Dingman J, Dalen JE. Changes in serum
cholesterol during the Stillman Diet. JAMA. 1974;228:54 –58.
23. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on
blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr.
1992;56:320 –328.
24. Stein F, Kolanowski J, Bemelmans S, Desmecht P. Renal handling of
calcium in fasting subjects: relation to ketosis and plasma ionized
calcium level. Scand J Clin Lab Invest. 1993;43(suppl 165):99 –100.
25. Heaney RP. Protein intake and the calcium economy. J Am Diet
Assoc. 1993;93:1259 –1260.
26. Freeman JM, Vining EPG, Pillas DJ, et al. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150
children. Pediatrics. 1998;102:1358 –1363.
27. Ballaban-Gil K, Callahan C, O’Dell C, et al. Complications of the
ketogenic diet. Epilepsia. 1998;39:744 –748.
28. Herzberg GZ, Fivsh BA, Kinsman SL, Gearhart JP. Urolithiasis associated with the ketogenic diet. J Pediatr. 1990;117:743–745.
29. Palgi A, Read JL, Greenberg I, et al. Multidisciplinary treatment of
obesity with a protein-sparing modified fast: results in 668 outpatients. Am J Public Health. 1985;75:1190 –1194.
30. Bistrian BR. Clinical use of a protein-sparing modified fast. JAMA.
1978;17:2299 –2302.
31. Clasey JL, Kanaley JA, Widemen L, et al. Validity of methods of
body composition assessment in young and older men and women.
J Appl Physiol. 1999;86:1728 –1738.
32. Heshka S, Greenway F, Anderson JW, et al. Self-help weight loss
versus a structured commercial program after 26 weeks: a randomized controlled study. Am J Med. 2000;109:282–287.
36
July 2002
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113
APPENDIX
Ingredients of Nutritional Supplementation
Multivitamin formula (administered daily in 6 capsules): Vitamin A as acetate (3000 IU), vitamin A as beta
carotene with mixed carotenoids (1200 IU), vitamin C
(360 mg), vitamin D3 (400 IU), vitamin E (300 IU), vitamin B1 (50 mg), vitamin B2 (50 mg), niacin (40 mg),
vitamin B6 (50 mg), folate (1600 mg), vitamin B12 (800
␮g), vitamin K (10 ␮g), biotin (600 ␮g), pantothenic acid
(120 mg), calcium (500 mg), magnesium (250 mg), zinc
(50 mg), selenium (200 ␮g), manganese (10 mg), chromium (600 ␮g), molybdenum (60 ␮g), potassium (20
mg), inositol hexanicotinate (100 mg), choline bitartrate
(100 mg), para amino benzoic acid (100 mg), vanadyl (80
␮g), n-acetyl-l-cysteine (120 mg), pantethine (150 mg),
quercetin (100 mg), boron (2 mg), grape seed extract (40
mg), green tea (80 mg). Unspecified amounts of lecithin
extracts, garlic, arginine, licorice, bromelain, pantethine,
spirulina, inulin, lactoferrin, bioperine, and acidophilus.
Essential oil formula (administered daily in 3 capsules): flaxseed oil (1200 mg), borage seed oil (1200 mg),
fish oil (1200 mg), vitamin E (15 IU).
Diet formula (administered daily in 6 capsules): Citrin (2700 mg), chromium (1200 ␮g), soy extract (9000
mg), methionine (1500 mg), l-carnitine (3000 mg), vitamin B6 (120 mg), pantethine (120 mg), asparagus (300
mg), parsley (300 mg), kelp (120 mg), spirulina (300 mg),
potassium citrate (594 mg), magnesium (360 mg), l-glutamine (450 mg), dl-phenylalanine (900 mg), l-tyrosine
(450 mg), piperine (30 mg).
`