Background:
The ability of modified alternate-day fasting (ADF; ie, consuming 25%
of energy needs on the fast day and ad libitum food
intake on the following day) to facilitate weight
loss and lower vascular disease risk in obese individuals remains
unknown.
Objective: This study examined the effects of ADF that is administered under controlled compared with self-implemented conditions on
body weight and coronary artery disease (CAD) risk indicators in obese adults.
Design: Sixteen obese subjects (12 women, 4 men) completed a 10-wk trial, which consisted of 3 phases: 1) a 2-wk control phase, 2) a 4-wk weight loss/ADF controlled food intake phase, and 3) a 4-wk weight loss/ADF self-selected food intake phase.
Results: Dietary
adherence remained high throughout the controlled food intake phase
(days adherent: 86%) and the self-selected food
intake phase (days adherent: 89%). The rate of
weight loss remained constant during controlled food intake (0.67 ± 0.1
kg/wk)
and self-selected food intake phases (0.68 ± 0.1
kg/wk). Body weight decreased (P < 0.001) by 5.6 ± 1.0 kg (5.8 ± 1.1%) after 8 wk of diet. Percentage body fat decreased (P < 0.01) from 45 ± 2% to 42 ± 2%. Total cholesterol, LDL cholesterol, and triacylglycerol concentrations decreased (P
< 0.01) by 21 ± 4%, 25 ± 10%, and 32 ± 6%, respectively, after 8 wk
of ADF, whereas HDL cholesterol remained unchanged. Systolic
blood pressure decreased (P < 0.05) from 124 ± 5 to 116 ± 3 mm Hg.
Conclusion: These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD risk. This
trial was registered at clinicaltrials.gov as UIC-004-2009.
INTRODUCTION
Obese individuals are at greater risk of developing coronary artery disease (CAD) (1). A decrease in energy intake by means of dietary restriction has been shown to lower the risk of CAD in obese populations
(2). The most common form of dietary restriction implemented is daily calorie restriction (CR), which requires individuals to
decrease their energy intake by 15–40% of baseline needs each day (3). Another form of dietary restriction used, although far less commonly, is alternate-day fasting (ADF) (4).
ADF regimens were created to increase adherence to dietary restriction
protocols because these regimens only require energy
restriction every other day rather than every day,
as with CR. ADF regimens consist of a “feed day” (ad libitum food intake
for 24 h) alternated with a “fast day” (complete
fast for 24 h). Modified ADF regimens that allow for the consumption of
20–25%
of energy needs on the fast day have also been
implemented.
To date, 3 ADF studies in humans have been performed (5–7). Results from the 2 trials performed in normal-weight men and women indicate that 2–3 wk of ADF (complete fast on the fast
day) significantly lowered body weight by 2.5% from baseline (5, 6). Decreases in triacylglycerol concentrations and increases in HDL-cholesterol concentrations were also observed (5, 6). Findings from the third trial conducted in overweight adults showed that 8 wk of modified ADF (20% restriction on the fast
day) significantly lowered body weight by ≈8% from baseline (7). This trial also showed LDL-cholesterol and triacylglycerol reductions of 10% and 40%, respectively, when posttreatment
values were compared with baseline (7). Whether or not these weight loss and cardioprotective effects can be reproduced in obese individuals by using ADF remains
unknown.
Nutrition intervention studies often provide participants with food to ensure that the trial is carefully controlled for energy
intake and macronutrient distribution (8).
At the conclusion of the study, when food is no longer provided, the
individual generally returns to their baseline food
intake/meal pattern. In some trials, dietary
counseling is provided to the participant at the end of the study to aid
the
subject in maintaining his or her newly acquired
healthy eating regimen (9). The ability of an obese individual to maintain an ADF regimen by providing the subject with dietary counseling, after a
period of controlled food intake, is of great interest but has yet to be tested.
Accordingly, this study examined the
ability of ADF to facilitate weight loss and beneficially modulate key
indicators of
CAD risk in obese men and women. Additionally, this
study compared the degree of weight loss that could be achieved by ADF
during a period of controlled food intake compared
with a period of self-selected food intake combined with dietary
counseling.
SUBJECTS AND METHODS
Subjects
Subjects were recruited from the
greater Chicago area by means of advertisements placed in community
centers and libraries.
A total of 52 individuals expressed interest in
the study, but only 20 were deemed eligible to participate after the
preliminary
questionnaire and body mass index (BMI; in kg/m2) assessment (Figure 1).
Key inclusion criteria were as follows: age 35–65 y, BMI between 30 and
39.9, weight stable for 3 mo before the beginning
of the study (ie, <5 kg weight loss or weight
gain), nondiabetic, no history of cardiovascular disease, lightly
active [ie,
<3 h/wk of light-intensity exercise at
2.5–4.0 metabolic equivalent tasks for 3 mo before the study (10)],
nonsmoker, and not taking weight loss or lipid- or glucose-lowering
medications. Perimenopausal women were excluded from
the study, and postmenopausal women (absence of
menses for >2 y) were required to maintain their current hormone
replacement
therapy regimen for the duration of the study.
The experimental protocol was approved by the Office for the Protection
of
Research Subjects at the University of Illinois,
Chicago, and all volunteers gave their written informed consent to
participate
in the trial.
FIGURE 1
Study flowchart. ADF, alternate-day fasting.
Study design
A 10-wk trial, which consisted of 3
consecutive intervention phases, was implemented to test the study
objectives. The 3 consecutive
phases were as follows: 1) 2-wk preloss control phase, 2) 4-wk weight loss/ADF controlled food intake phase, and 3) 4-wk weight loss/ADF self-selected food intake phase.
Phase 1: preloss control protocol
During the first phase, subjects were required to keep their body weight stable by maintaining their usual eating and exercise
habits. As such, each subject served as his or her own control.
Phase 2: weight loss/ADF controlled food intake protocol
The second phase consisted of a 4-wk controlled food intake ADF period. The baseline energy requirement for each subject was
determined by the Mifflin equation (11).
All subjects consumed 25% of their baseline energy needs on the “fast”
day (24 h) and then consumed food ad libitum on
each alternate “feed” day (24 h). During this
controlled food intake phase, subjects were provided with a
calorie-restricted
meal on each fast day, and consumed food ad
libitum at home on the alternate day. All meals were prepared in the
metabolic
kitchen of the Human Nutrition Research
Center at the University of Illinois, Chicago, and were provided as a
3-d rotating
menu. The nutrient composition of the
provided fast day meal is shown in Table 1.
On the ad libitum food intake day, subjects were instructed to limit
fat intake to <30% of energy needs by choosing low-fat
meat and dairy options. The feed/fast days
began at midnight each day, and all fast day meals were consumed between
1200 and
1400 to ensure that each subject was
undergoing the same duration of fasting. On each fast day, the subjects
were allowed
to consume energy-free beverages, tea,
coffee, and sugar-free gum and were encouraged to drink plenty of water.
View this table:
TABLE 1
Nutrient composition of fast day meals during the controlled food intake phase1
Phase 3: weight loss/ADF self-selected food intake protocol
The third phase consisted of a 4-wk
ADF self-selected food intake period in conjunction with weekly dietary
counseling. During
this phase, subjects still consumed 25% of
their baseline energy needs on the fast day and consumed food ad libitum
on the
feed day. However, during this period, no
food was provided to the subjects. Instead, subjects met with a
registered dietitian
at the beginning of each week to learn how to
maintain the ADF regimen on their own at home. During each counseling
session,
the dietitian worked with the subject to
develop individualized fast day meal plans. These plans included menus,
portion sizes,
and food lists that were consistent with
their food preferences and prescribed calorie levels for the fast day.
During these
sessions, subjects were also instructed how
to make healthy food choices on the ad libitum food intake days by
choosing low-fat
meat and dairy options. Subjects were asked
to consume fast day meals between 1200 and 1400.
Blood collection protocol
Twelve-hour fasting blood samples were
collected between 0700 and 0900 at baseline (day 1), at the end of
phase 1 (day 14),
at the end of phase 2 (day 41: feed day; day 42:
fast day), and at the end of phase 3 (day 69: feed day; day 70: fast
day).
The subjects were instructed to avoid exercise,
alcohol, and coffee for 24 h before each visit. Blood was centrifuged
for
15 min at 520 × g at 4°C to separate plasma from red blood cells and was stored at −80°C until analyzed.
Analyses
Adherence to ADF diets
During phase 2 (controlled food
intake phase), subjects were instructed to eat only the fast day food
provided and to report
any extra food item consumed by using an
“extra food log.” During phase 3, subjects were provided with
individualized meal
plans that were consistent with their food
preferences and prescribed calorie levels for the fast day. Subject was
asked to
report any extra food item consumed on the
fast day that did not comply with their prescribed plan by using the
extra food
log. The log was collected and reviewed by
study personnel each week. If the log indicated that the subject ate an
extra food
item on a fast day, that day was labeled as
“not adherent.” If the log revealed that the subject did not eat any
extra food
item, that day was labeled as “adherent.”
Adherence data were assessed each week as 1) absolute adherence (number of days adherent with diet) and 2) percentage adherence calculated by applying the following formula:
Weight loss and percentage body fat assessment
Body weight measurements were taken
to the nearest 0.5 kg at the beginning of every week with subjects
wearing light clothing
and without shoes by using a balance beam
scale at the research center (HealthOMeter; Sunbeam Products, Boca
Raton, FL). BMI
was assessed as kilograms divided by meters
squared. Percentage body fat was assessed in triplicate after the
weigh-in by
using a tetra-polar bioelectrical impedance
analyzer (Omron HBF-500; Omron Health Care, Bannockburn, IL) (12). The within-group CV for percentage body fat was 2.7%.
Plasma lipid profile, blood pressure, and heart rate determination
Plasma total cholesterol,
HDL-cholesterol, and triacylglycerol concentrations were measured in
duplicate by using enzymatic
kits, standardized reagents, and standards
(Biovision Inc, Mountainview, CA) and analyzed by using a microplate
reader (iMark
Microplate Reader; Bio-Rad Laboratories Inc,
Richmond, CA). The concentration of LDL cholesterol was calculated by
using the
Friedewald, Levy, and Fredrickson equation (13).
The within-group CVs for total cholesterol, HDL-cholesterol, and
triacylglycerol concentrations were 3.1%, 2.6%, and 2.5%,
respectively. Blood pressure and heart rate
were measured in triplicate with the subject in a seated position after a
10-min
rest.
Statistics
Results are presented as means ± SEMs. Tests for normality were included in the model. Sample size was calculated by assuming
a 10% change in LDL-cholesterol concentrations, with a power of 80% and an α risk of 5%. One-factor analysis of variance was performed to determine an overall P value for each variable.
Bonferroni correction was used to
assess significance. Relations between continuous variables were
assessed by using simple
regression analyses as appropriate. Data were
analyzed by using SPSS software (version 17.0 for Mac OS X; SPSS Inc,
Chicago,
IL).
RESULTS
Subject dropout and baseline characteristics
Twenty subjects commenced the study,
with 16 completing the entire 10-wk trial. Two subjects dropped out due
to time constraints,
whereas 2 others dropped out due to inability to
comply with the ADF protocol. Baseline characteristics of the subjects
who
completed the entire 10-wk trial are shown in Table 2.
View this table:
TABLE 2
Characteristics at baseline in subjects who completed the 10-wk trial (n = 16)
Adherence to ADF diets
During the ADF controlled food intake
phase, subjects were adherent with the provided fast day meals (ie, no
extra food items
consumed) for 3.8 ± 0.1 of 4 d during week 3,
2.6 ± 0.1 of 3 d during week 4, 3.6 ± 0.1 of 4 d during week 5, and 2.1 ±
0.2
of 3 d during week 6. During the ADF
self-selected food intake phase, subjects were adherent with prescribed
kcal goal for
3.5 ± 0.2 of 4 d during week 7, 2.5 ± 0.2 of 3 d
during week 8, 3.8 ± 0.1 of 4 d during week 9, and 2.8 ± 0.1 of 3 d
during
week 10. When expressed as percentage adherence (Figure 2),
there was no drop in adherence over the course of the controlled food
intake phase or the self-selected food intake phase.
Moreover, no changes in physical activity habits
were reported over the course of the trial; thus, changes in body
weight
and clinical parameters may be attributed
primarily to change in diet.
FIGURE 2
Mean (±SEM) body weight and percentage adherence during the 10-wk trial. A: Body weight of subjects (n = 16) at each week. B: Percentage adherence values of subjects (n = 16) on the fast day at each week. Percentage adherence was calculated as shown in Equation 1. There was no difference in percentage adherence between weeks during the 10-wk trial. ADF, alternate-day fasting. Overall
P value (P = 0.0001 for
body weight) was calculated with the use of one-factor ANOVA. Values
with different superscript letters are significantly
different, P < 0.05 (Bonferroni analysis).
Weight loss and change in percentage body fat by ADF
During the preloss control phase, body weight of the subjects remained stable (Figure 2).
Throughout the ADF controlled food intake phase, there was a mean body
weight loss of 0.67 ± 0.1 kg/wk. This rate of weight
loss remained consistent during the ADF
self-selected food intake phase (0.68 ± 0.1 kg/wk). Total weight loss (P < 0.001) over the course of the trial was 5.8 ± 1.1% from baseline (5.6 ± 1.0 kg). Mean BMI of the subjects at baseline was
33.7 ± 1.0. At the end of the controlled food intake phase, BMI decreased (P < 0.001) to 32.8 ± 1.0, and by the end of the self-selected food intake phase, BMI further decreased (P < 0.01) to 29.9 ± 2.1. At baseline, mean percentage body fat was 45.0 ± 1.6%. Percentage body fat was not changed after 4
wk (43.3 ± 2.1%) but was reduced (P < 0.01) after 8 wk of ADF (42.1 ± 2.0%). Fat mass decreased (P < 0.01) by 5.4 ± 0.8 kg after 8 wk of diet, whereas changes in fat-free mass were not significant (−0.1 ± 0.1 kg). Rate of
weight loss was related to percentage of days adherent to diet per week (r = 0.43, P < 0.05).
Changes in plasma lipids by ADF
Mean plasma lipid concentrations over the 10-wk trial are presented in Table 3 (values presented in the text are an average of the food intake and fast days). Total cholesterol concentrations were lowered
(P < 0.001) by 18.0 ± 4.3% after
completion of the controlled food intake phase and by 21.2 ± 4.3% after
completion of the self-selected
food intake phase. Lowered LDL cholesterol (P < 0.01) was noted after 4 and 8 wk of ADF (26.0 ± 8.2% and 24.8 ± 9.6%, respectively). HDL-cholesterol concentrations were
not affected by the ADF diet. Circulating triacylglycerol concentrations were lowered (P < 0.01) by 25.3 ± 7.0% after the controlled food intake phase and further lowered (P
< 0.01) by 32.2 ± 6.4% after the self-selected food intake phase. No
differences between food intake and fast day values
were observed for any lipid parameter. Decreases
in LDL cholesterol were associated with decreased body weight (r = 0.48, P < 0.05) posttreatment. Decreased triacylglycerol concentrations were related to reductions in body weight (r = 0.45, P < 0.05) and percentage body fat (r = 0.38, P < 0.05) at the end of the study.
View this table:
TABLE 3
Plasma lipid concentrations at baseline and at the end of each phase of the trial1
Changes in blood pressure and heart rate by ADF
The effects of 8 wk of ADF on blood pressure and heart rate were also assessed. Systolic blood pressure was lowered (P
< 0.05) by 4.4 ± 1.8% after completion of the controlled food intake
phase and by 5.1 ± 1.6% after completion of the self-selected
food intake phase (Figure 3).
No differences between food intake and fast day values were observed
for systolic blood pressure. Diastolic blood pressure
values at baseline (80.3 ± 2.7 mm Hg) did not
differ from those at week 6 (79.2 ± 2.1 mm Hg) or from those at week 10
(78.8
± 2.5 mm Hg). Heart rate was significantly
lowered (P < 0.05) from baseline after 8 wk of diet (Figure 3). Changes in body weight, BMI, and percentage body fat were not related to blood pressure or heart rate values.
FIGURE 3
Mean (±SEM) systolic blood pressure and heart rate during each phase of the 10-wk trial. A: Systolic blood pressure values
of subjects (n = 16) at each week. B: Heart rate values of subjects (n = 16) at each week. ADF, alternate-day fasting. Overall P values (P = 0.009 for blood pressure; P =
0.012 for heart rate) were calculated with the use of one-factor ANOVA.
Values with different superscript letters are significantly
different, P < 0.05 (Bonferroni analysis).
DISCUSSION
This study is the first to show that ADF
is an effective dietary intervention to help obese individuals lose
weight and lower
CAD risk. Specifically, we show here that an ADF
regimen, which allowed participants to consume 25% of their energy needs
on the fast day, resulted in a mean weight loss of
5.8% from baseline after only 8 wk of treatment. Decreases in several
key
biomarkers for CAD risk, such as total cholesterol,
LDL cholesterol, triacylglycerols, systolic blood pressure, and heart
rate, were also observed. Additionally, we show
here that a similar rate of weight loss was achieved during the ADF
controlled
food intake period when compared with the ADF
self-selected food intake period. These data suggest that subjects were
able
to maintain the ADF meal pattern when preparing
their own meals at home (ie, when removed from a clinically controlled
environment).
Although CR is more frequently implemented than ADF to facilitate weight loss (4, 14), many obese patients find it difficult to adhere to CR because food intake must be limited every day by 15–40% of baseline
needs (15–17). ADF regimens were created to increase adherence to dietary restriction protocols because these regimens require energy
restriction only every other day (4).
In the present study, we measured the ability of obese subjects to
adhere to their fast day energy goal. Our data show
that adherence to ADF was high (days per week
adherent: ≈85%) and that this level of adherence remained constant
throughout
the 8-wk trial. We also show here that adherence to
the ADF protocol was similar between the controlled food intake phase
and the self-selected food intake phase. These
findings suggest that obese individuals are capable of self-selecting
foods
to meet their individual fast day energy goals. It
should be noted, however, that the subjects met weekly with a registered
dietitian. In view of this, future studies should
examine the ability of obese subjects to adhere to ADF regimens without
the help of a dietitian. Such data would be more
indicative of the efficacy of the ADF regimen for weight loss in the
general
population. It should also be noted that of the 20
subjects initially recruited to partake in the study, 2 individuals
dropped
out due to inability to comply with the fast day
diet protocol. Thus, on the basis of these findings, it is possible that
this dietary restriction protocol may not be well
tolerated by 10% (or possibly more) of the obese population.
Nevertheless,
dropout rate data from ADF trials with larger
sample sizes (eg, n = 68 subjects, calculated with a power of 80% and an α
risk of 5%) are still required before solid conclusions can be reached.
It should also be noted that this trial was not controlled.
The need for a randomized controlled trial to test
similar hypotheses is clearly warranted.
Decreases in body weight are directly related to degree of dietary adherence (17–20).
In the present ADF study, obese subjects lost an average of 0.68 kg/wk,
which corresponded to a total weight loss of 5.6
kg over 8 wk (95% CI: −7.4, −3.8). Because rate of
weight loss was correlated to percentage weekly adherence, it can be
assumed
that the high adherence rate to ADF diets played a
significant role in the total weight loss achieved. We also show here
that
rate of weight loss remained constant after the
subjects switched from the ADF controlled food intake phase to the ADF
self-selected
food intake phase. Thus, the ADF diet may be an
effective dietary strategy to help obese individuals achieve a stable,
healthy
rate of weight loss, even during periods of
self-implementation. We predicted that subjects would lose a total of
4.5 kg fat
mass after 8 wk (on the basis of a 75% decrease in
energy intake on the fast day, with no change in energy intake on the
feed
day). The actual fat mass lost (5.4 kg) exceeded
our predictions. This indicates that these subjects were also limiting
their
energy intake on the feed day, which may have
occurred because the subjects knew they were enrolled in a weight loss
trial.
Our weight loss findings are similar to those of
Johnson et al (7) (8% weight loss after 8 wk of ADF in overweight individuals). However, the trial by Johnson et al (7) takes precedence both in time and study design because it was a randomized controlled trial study. The degree of weight
loss achieved by the present ADF regimen is also comparable to that of short-term CR trials (14, 21, 22).
In view of these similar effects on body weight, ADF may be considered a
suitable alternative to CR to help obese individuals
lose weight. A study that directly compares the
effects of ADF to that of CR on body weight and body composition is
undoubtedly
an important next step in the ADF field. It must
also be noted, however, that the degree of weight loss achieved by ADF
may
not be sustainable long term. Whether or not obese
individuals are able to adhere to ADF over the long term and experience
sustained weight loss will be an important focus of
future research.
Beneficial modulations in several key CAD
risk indicators were also noted in response to ADF. Total and
LDL-cholesterol concentrations
decreased by 21% and 25%, respectively, after 8 wk
of diet. Triacylglycerol concentrations were also lowered by 32% when
baseline
values were compared with posttreatment values.
These modulations in LDL-cholesterol and triacylglycerol concentrations
are
similar to those observed by Johnson et al (7).
We also show that improvements in plasma LDL-cholesterol and
triacylglycerol concentrations were correlated to changes
in body weight and percentage body fat
posttreatment. Thus, the degree of weight loss achieved by this ADF
regimen most likely
played a major role in the degree to which these
plasma lipids were altered (23).
No changes in HDL-cholesterol concentrations were observed throughout
the trial. This lack of effect of ADF on HDL cholesterol
is not surprising because this cardioprotective
lipid parameter is generally augmented only in response to exercise
training
(24).
An important next step in the ADF field will be to incorporate an
exercise program into this lifestyle regimen. Perhaps
with the addition of physical activity,
HDL-cholesterol concentrations will increase, thus beneficially
modulating the entire
lipid profile. Findings from the majority of CR
trials also report no change in HDL cholesterol after short durations of
treatment
(21, 22, 25).
Lipid variable measurements were assessed on consecutive food intake
and fast days at the end of each diet phase (after
a 12-h fasting blood draw). Results reveal that
consumption of food or fasting the day before the lipid assessment has
no
effect on lipid concentrations. Findings from the
present study also show that 8 wk of ADF in obese individuals may reduce
systolic blood pressure and heart rate. In view of
the powerful association of high blood pressure with risk of CAD (26, 27), this finding further supports the cardioprotective actions of ADF.
In summary, our findings indicate that
ADF may be implemented as an effective diet strategy to help obese
individuals lose
weight and to confer protection against CAD. ADF
should therefore be considered a viable option for obese patients who
wish
to lose weight through dietary restriction but who
are unable to adhere to daily CR.
Acknowledgments
The authors’ responsibilities were as
follows—KAV: designed the experiment, analyzed the data, and wrote the
manuscript; SB
and ECC: conducted the clinical trial, performed
the laboratory analyses, and assisted with the preparation of the
manuscript;
and MCK: coordinated food preparation and
distribution, provided technical assistance during the analysis phase of
the experiment,
and assisted with the preparation of the
manuscript. The authors had no conflicts of interest to report.
- Received July 12, 2009.
- Accepted September 1, 2009.
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