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Alternate-day fasting in nonobese subjects: Effects on body weight, body composition, and energy metabolism


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Prolonged dietary restriction increases the life span in rodents. Some evidence suggests that alternate-day fasting may also prolong the life span. Our goal was to determine whether alternate-day fasting is a feasible method of dietary restriction in nonobese humans and whether it improves known biomarkers of longevity. Nonobese subjects (8 men and 8 women) fasted every other day for 22 d. Body weight, body composition, resting metabolic rate (RMR), respiratory quotient (RQ), temperature, fasting serum glucose, insulin, free fatty acids, and ghrelin were assessed at baseline and after 21 d (12-h fast) and 22 d (36-h fast) of alternate-day fasting. Visual analogue scales were used to assess hunger weekly. Subjects lost 2.5 +/- 0.5% of their initial body weight (P < 0.001) and 4 +/- 1% of their initial fat mass (P < 0.001). Hunger increased on the first day of fasting and remained elevated (P < 0.001). RMR and RQ did not change significantly from baseline to day 21, but RQ decreased on day 22 (P < 0.001), which resulted in an average daily increase in fat oxidation of > or =15 g. Glucose and ghrelin did not change significantly from baseline with alternate-day fasting, whereas fasting insulin decreased 57 +/- 4% (P < 0.001). Alternate-day fasting was feasible in nonobese subjects, and fat oxidation increased. However, hunger on fasting days did not decrease, perhaps indicating the unlikelihood of continuing this diet for extended periods of time. Adding one small meal on a fasting day may make this approach to dietary restriction more acceptable.
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Alternate-day fasting in nonobese subjects: effects on body weight,
body composition, and energy metabolism
Leonie K Heilbronn, Steven R Smith, Corby K Martin, Stephen D Anton, and Eric Ravussin
Background: Prolonged dietary restriction increases the life span in
rodents. Some evidence suggests that alternate-day fasting may also
prolong the life span.
Objective: Our goal was to determine whether alternate-day fasting
is a feasible method of dietary restriction in nonobese humans and
whether it improves known biomarkers of longevity.
Design: Nonobese subjects (8 men and 8 women) fasted every other
day for 22 d. Body weight, body composition, resting metabolic rate
(RMR), respiratory quotient (RQ), temperature, fasting serum glu-
cose, insulin, free fatty acids, and ghrelin were assessed at baseline
and after 21 d (12-h fast) and 22 d (36-h fast) of alternate-day fasting.
Visual analogue scales were used to assess hunger weekly.
Results: Subjects lost 2.5 0.5% of their initial body weight (P
0.001) and 4 1% of their initial fat mass (P 0.001). Hunger
increased on the first day of fasting and remained elevated (P
0.001). RMR and RQ did not change significantly from baseline to
day 21, but RQ decreased on day 22 (P 0.001), which resulted in
an average daily increase in fat oxidation of 15 g. Glucose and
ghrelin did not change significantly from baseline with alternate-day
fasting, whereas fasting insulin decreased 57 4% (P 0.001).
Conclusions: Alternate-day fasting was feasible in nonobese sub-
jects, and fat oxidation increased. However, hunger on fasting days
did not decrease, perhaps indicating the unlikelihood of continuing
this diet for extended periods of time. Adding one small meal on a
fasting day may make this approach to dietary restriction more
acceptable. Am J Clin Nutr 2005;81:69 –73.
KEY WORDS Resting metabolic rate, fat oxidation, insulin,
glucose, biomarkers of longevity
Prolonged dietary restriction (DR) is the only proven method
of increasing the life span in rodents, flies, yeast, and worms (1).
The mechanism or mechanisms by which DR increases life span
are unclear, but the effects of DR include reduced metabolic rate,
reduced oxidative damage, altered neuroendocrine signaling,
and improved insulin sensitivity (2). The effect of prolonged DR
on the life span in nonhuman primates is currently being inves-
tigated (3–5). Although conclusive results are years away, many
improvements in biomarkers of longevity, including reduced
core temperature, resting metabolic rate (RMR), dehydroepi-
androsterone sulfate, glucose, and insulin, have already been
observed. Prolonged DR also alters the expression of many genes
from skeletal muscle, brain, and liver, including genes encoding
heat shock proteins and uncoupling proteins and genes involved
in oxidative damage (6 8). Recent microarray results in mouse
liver indicate that there is significant overlap of genes that are
up-regulated by short-term starvation and by prolonged DR (9).
Alternate-day fasting may therefore be an alternative to pro-
longed DR as a method of increasing maximal life span. Good-
rick et al (10) found that alternate-day fasting increased median
and maximal life span in C57Bl/6 mice when it was introduced
at 1.5 and 6 mo of age and increased maximal, but not median, life
span in A/J mice. Recently, Anson et al (11) observed that mice
fed every other day consumed the same total energy as did ad
libitum fed animals and had similar body weights but had re-
duced glucose and insulin concentrations and increased resis-
tance to endotoxic stress (11).
A pilot study testing the feasibility and effects of long-term DR
on biomarkers of longevity in nonobese humans is currently
under investigation. This randomized clinical trial named
CALERIE (sponsored by the National Institute of Aging) is
testing numerous behavioral strategies and diets (ranging from
liquid energy to 20–30% DR to increased energy expenditure by
physical activity) to determine which of these will prove the most
viable in today’s “obesogenic” environment. However, the fea-
sibility and efficacy of alternate-day fasting is not being inves-
tigated. Given the difficulty that individuals have in estimating
energy intake (12–14), alternate-day fasting may prove to be a
less complicated method than prolonged DR in humans. Indeed,
one study investigated the effects of alternate-day DR for 3 y
(15). In that study, the subjects were allowed1Lofmilk and 2–3
pieces of fruit on their energy-restricted day and 9600 kJ/d on the
other day. The control group was fed 9600 kJ/d every day. The
subjects randomly assigned to alternate-day DR spent less time
in the infirmary and had a lower death rate than in the control
group (6 versus 13; NS) (16). The present study was undertaken
to determine the feasibility of alternate-day fasting in nonobese
subjects. In addition, the effects of alternate-day fasting on body
weight, RMR, fat oxidation, and biomarkers of longevity were
From the Pennington Biomedical Research Center, Baton Rouge, LA.
Reprints not available. Address correspondence to E Ravussin, Penning-
ton Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA,
70808. E-mail:
Received May 27, 2004.
Accepted for publication September 2, 2004.
69Am J Clin Nutr 2005;81:69–73. Printed in USA. © 2005 American Society for Clinical Nutrition
by guest on June 6, 2013ajcn.nutrition.orgDownloaded from
Healthy, nonobese [body mass index (in kg/m
) range: 20.0
30.0] men (n ҃ 8) and women (n ҃ 8) aged between 23 and 53 y
were recruited (Table 1). The subjects had different levels of
physical activity: 7 were sedentary, 3 were moderately active
(exercised 1–2 times/wk), and 6 were quite active (exercised 4 –5
times/wk). Competitive athletes and subjects with type 2 diabe-
tes were excluded. The Institutional Review Board of the Pen-
nington Biomedical Research Center approved the study, and the
subjects gave their written informed consent.
Study design
The subjects attended the clinical research center on 2 con-
secutive days at baseline (days Ҁ2 and Ҁ1) and on 2 consecutive
days after 3 wk of alternate-day fasting following a “feast” day
(day 21) and following a “fast” day (day 22). The subjects had
therefore fasted 12 h (overnight) on days Ҁ2, Ҁ1, and 21 and 36 h
on day 22. The subjects were instructed to avoid exercise, alco-
hol, and coffee for 24 h before each visit. At each visit, the
subjects arrived in the clinic at 0700 and were weighed while
wearing a hospital gown. Blood pressure was measured with the
subject in a seated position after a 5-min rest, oral temperature
was recorded (SureTemp; Welch Allyn Inc, NY), and a fasting
blood sample was drawn. RMR was measured for 30 min with a
DeltaTrac metabolic monitor (SensorMedics, Yorba Linda, CA)
after a 20-min resting period while the subjects were awake in a
semirecumbent position. On days Ҁ2 and 21, body composition
was measured by dual-energy X-ray absorptiometry (QDR 4500;
Hologic Inc, Bedford, MA). At baseline and on days 1, 7, 15, and
21 (fasting days), the subjects completed visual analogue scales
(VASs) at 1000, 1200, 1400, and 1600 to assess their feelings of
hunger, fullness, desire to eat, satisfaction, and prospective food
consumption (17). Briefly, the participants were asked to place a
mark on a 100-mm line anchored by “not at all” and “extremely”
to record subjective levels of hunger or satiety. The VASs were
scored by measuring from the left end of the line to the mark in
mm, and mean ratings were calculated for each day. At baseline,
the subjects also completed the Eating Inventory questionnaire,
which assessed dietary restraint (the intent and ability to restrict
caloric intake), disinhibition (the tendency to overeat), and hun-
ger (18). The subjects also completed a nine-item self-report
questionnaire, which was developed for this study, to assess
eating attitudes and behaviors with the use of an 8-point scale.
This questionnaire (Eating Behaviors Questionnaire) assessed
whether the subjects consider themselves “dieters” who watch
what they eat or “big eaters” who tend to eat 1 or 2 large meals per
After baseline testing was completed, the subjects fasted from
midnight to the subsequent midnight on alternating days for 22 d.
On each fasting day, the subjects were allowed to consume
energy-free beverages, tea, coffee, and sugar-free gum and were
instructed to keep their water intake high. On each feasting day,
the subjects were instructed to eat whatever they wished and were
informed that double their usual food intake would be required to
maintain their usual body weight. The subjects were provided
with calibrated digital scales (Tanita, Arlington Heights, IL) to
record their morning fasting body weight, urinary sticks to test
for the presence of ketones, and a diet diary to record anything
that was consumed on the fasting day. On day 20, the subjects
were required to fast from 1900 so that a 12-h overnight fast
would be completed before testing began the following morning
at 0700. They did not break this fast until after their clinic visit on
day 22.
Biochemical analytes
Glucose was analyzed by using a glucose oxidase electrode
(Syncron CX7; Beckman, Brea, CA). Free fatty acids were mea-
sured on a Synchron CX5 by using reagents from Wako (Rich-
mond, VA).
-Hydroxybutyrate was measured on a Synchron
CX5 by using reagents from Sigma (St Louis). Insulin was mea-
sured by using an immunoassay on a DPC 2000 (Diagnostic
Product Corporation, Los Angeles). Ghrelin was measured by
using a radioimmunoassay kit from Linco (St Charles, MO).
Statistical analysis
Data are expressed as means SEMs. SAS 8.2 (SAS Institute
Inc, Cary, NC) and SPSS 11.0.1 (SPSS Inc, Chicago) were used
for data analysis. Baseline measures (days Ҁ2 and Ҁ1) were
averaged. Statistics were performed by one- and two-factor
repeated-measures analysis of variance. Post hoc analysis was
performed with Tukey’s tests where necessary. RMR was ana-
lyzed by using linear regression to adjust for fat mass and fat-free
mass. Correlations were performed with Pearson’s correlation
coefficient. Significance was set at P 0.05. Fasting insulin
values below the detection limit of the assay (2.0 mU/L) were
assigned a value of 1.0 mU/L. Insulin values were log trans-
formed for analysis.
The subjects’ characteristics by sex are given in Table 1. On
the basis of their self-recorded diet diaries and weight logs (Fig-
ure 1), the subjects complied with the protocol. Urinary ketones
were not useful as a measure of compliance because they were
not consistently detected in all subjects (data not shown). On the
basis of daily regressed body weights, the subjects lost 2.5
0.5% of their initial body weight. This self-reported weight loss
was confirmed by weights measured in the clinic at baseline and
on days 21 and 22 (P 0.001). Significant reductions were
observed in fat mass (P 0.001) and fat-free mass (P 0.05)
after the intervention (Figure 1).
Baseline characteristics of the participants by sex
(n ҃ 8)
(n ҃ 8)
Age (y) 34 330 1
Weight (kg) 80.6 4.4 59.7 1.7
BMI (kg/m
25.2 1.1 22.6 0.6
Fat mass (%) 22 225 1
Cholesterol (mmol/L) 4.9 0.4 4.7 0.2
HDL (mmol/L) 1.0 0.1 1.8 0.1
Triacylglycerols (mmol/L) 2.5 0.6 1.1 0.1
Systolic blood pressure (mm Hg) 116 2 104 3
Diastolic blood pressure (mm Hg) 75 368 2
All values are x SEM.
Significantly different from men, P 0.01 (one-factor ANOVA).
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On average, the men considered themselves “big eaters,” and
the women reported that they “watched what they ate.” Percent-
age weight loss did not differ significantly between the men and
the women, but weight loss correlated negatively with consider-
ing oneself a big eater after adjustment for sex (r ҃Ҁ0.63, P ҃
0.04). The dietary restraint and disinhibition scales of the Eating
Inventory questionnaire did not significantly predict weight loss.
VASs were completed for all days by only 8 of 16 subjects.
First, baseline results were compared with the first day of fasting.
As expected, a significant increase was found in feelings of
hunger (from 37 5to56 4 mm; P 0.001), and a significant
decrease was noted in feelings of fullness (from 43 3to23
4 mm; P 0.001). However, repeated-measures analysis over
time (days 1, 7, 15, and 21) showed no significant changes in the
subjects’ perception of hunger, thirst, desire to eat, or feelings of
satisfaction, although feelings of fullness increased slightly over
time (P 0.05).
Temperature (data not shown) and absolute and relative rest-
ing metabolic rate (adjusted for fat-free mass and fat mass) were
not significantly different from baseline (Table 2). Respiratory
quotient (RQ) was also not significantly different from baseline
at day 21; however, RQ was lower on day 22 (P 0.001; Table
2). More specifically, fat oxidation increased from 64 g/24 h at
baseline to 101 g/24 h, and carbohydrate oxidation decreased
from 175 to 81 g/24 h. The change in RQ from baseline to day 21
was related to weight loss (r ҃Ҁ0.76, P 0.001).
The women had significantly lower glucose, insulin, free fatty
acid, triacylglycerol, and LDL-cholesterol concentrations and
significantly higher HDL-cholesterol and ghrelin concentrations
than did the men (P 0.05). Fasting glucose was not signifi-
cantly changed from baseline in the men or the women (Figure
2). Fasting insulin was lower on day 22 in both the men and the
women (P 0.001), and fasting
-hydroxybutyrate and free
fatty acid concentrations were higher on day 22 in both the men
and the women (Figure 2; P 0.001). Fasting ghrelin was not
significantly altered from baseline on day 21 (results not shown)
or day 22 (from 1019 128 to 1063 158 pg/mL in the men and
from 1403 63 to 1493 139 pg/mL in the women). Systolic
and diastolic blood pressure were not significantly altered by the
intervention (data not shown). HDL was elevated from baseline
in the women only (P 0.001; data not shown), and triacylglyc-
erol was significantly reduced from baseline in the men only (P
0.05; data not shown).
Alternate-day fasting may be an alternative to prolonged DR
for increasing the life span (11). In the present study, we report
that alternate-day fasting is feasible for short time periods in
nonobese subjects. One participant reported feeling lightheaded
once, and 4 subjects reported constipation. No subjects withdrew
during the study, but many reported feeling irritable on their
fasting days, perhaps indicating the unlikelihood of continuing
this diet for extended periods of time. The results from the VASs
suggest that feelings of fullness may have increased from the first
fasting day over the course of the study, but other subjective
states related to food intake motivation did not habituate, includ-
ing hunger. This result contrasts with the results of studies using
liquid-based, very-low-energy diets where hunger diminishes
despite a marked energy deficit (19). Overall, these results sug-
gest that a prolonged schedule of fasting and feasting would be
marred by aversive subjective states (eg, hunger and irritability),
which would likely limit the ability of most individuals to sustain
this eating pattern.
This is the first study, to our knowledge, to test the effects of
alternate-day fasting on body weight and other metabolic vari-
ables in humans. Body weight was clearly reduced from baseline
after 3 wk of alternate-day fasting, indicating that the subjects
were unable to consume enough food on the feasting days to
FIGURE 1. Top panel: mean (SEM) percentage change in daily self-
recorded body weight (n ҃ 16). Body weight was measured before breaking
an overnight fast (odd days) or after 24 –36-h fasts (even days). Bottom panel:
mean (SEM) fat mass (FM) and fat-free mass (FFM) by dual-energy X-ray
absorptiometry measured after 12-h fasts at baseline (day Ҁ2) and on day 21.
Significantly different from baseline, P 0.001 for FM and P 0.05 for
FFM (one-factor ANOVA).
Resting metabolic rate (RMR), respiratory quotient (RQ), and fat and
carbohydrate oxidation measured at baseline and after a fed day (day 21)
and a fast day (day 22)
Baseline Day 21 Day 22
RMR (kJ/d) 6675 283 6292 268 6329 260
RQ 0.85 0.01 0.86 0.02 0.79 0.01
Fat oxidation (g/24 h)
64 854 10 101 9
Carbohydrate oxidation (g/24 h)
175 17 184 24 81 16
All values are x SEM. Two consecutive days at baseline were
averaged for analysis.
Significantly different from baseline, P 0.001 (one-factor repeated-
measures ANOVA).
Calculated by assuming that protein oxidation was 15% of RMR.
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maintain their weight. This is opposite the results observed in
rodents, where mice fed every other day maintained their body
weight and consumed roughly the same amount of food in 1 d that
ad libitum–fed animals consumed over 2 d (11). We hypothe-
sized that the subjects with a self-reported ability to overeat or eat
large amounts of food would maintain their body weight, and this
hypothesis was supported: considering oneself a “big eater” was
negatively associated with weight loss when sex was controlled
for by partial correlation. Whether alternate-day fasting would
lead to weight loss in obese participants remains unclear. The
negative subjective states associated with the study cast doubt on
the ability of individuals to voluntarily engage in alternate-day
fasting for prolonged periods of time. Altering the clock time that
the subjects are asked to fast (eg, from 1900 to 1900) or adding
a small meal (10 –20% of caloric needs) to the fasting day may
make alternate-day fasting more acceptable in all populations.
Ghrelin is a peptide secreted in the gut that is reduced on
feeding and has been implicated in the regulation of feeding
behavior and energy balance. Obese subjects have lower fasting
ghrelin concentrations than do lean subjects (20) but have im-
paired suppression of plasma ghrelin in response to a meal (21).
Furthermore, ghrelin is increased after weight loss in obese sub-
jects (22, 23), perhaps driving the common phenomenon of
weight regain after weight loss. In the present study, the women
had significantly higher ghrelin concentrations than did the men.
This has been reported previously (24) but is not consistently
observed (25) and may be related to central adiposity. In contrast
with the large increases in reported hunger, plasma ghrelin was
unchanged in both the men and the women, even after 36 h of
fasting. Studies in rodents have found that 24-h fasts increase
plasma ghrelin (26). However, fasting for 72 h did not change
plasma ghrelin in lean men (24). The results of these fasting
studies in humans call into question the role of ghrelin in the
hunger drive and highlight the need for further research in this
A hallmark of rodent studies of longevity is reduced fasting
glucose and insulin concentrations and increased insulin sensi-
tivity in dietary-restricted animals (27). Reduced fasting insulin
has also been associated with increased longevity in humans
(27). In the present study, insulin was reduced after a fast day,
suggesting improved insulin sensitivity. However, plasma free
fatty acids were also elevated after fasting; these elevated con-
centrations may impair insulin-mediated glucose disposal and
the suppression of hepatic glucose production (28). We also
found that alternate-day fasting did not significantly change fast-
ing glucose or insulin from baseline after a 12-h fast. This is in
contrast with results in mice, in which glucose and insulin con-
centrations were lower after 14-h fasts than in ad libitum fed–
mice or mice fed energy-restricted diets. Thus, humans may need
to fast for longer than 12 h for this effect to be observed. Alter-
natively, this could be due to the already low glucose concentra-
tions of our population or that 3 wk of alternate-day fasting was
insufficient to produce this response. The study design may also
have affected these results, because the subjects anecdotally re-
ported eating even more than usual on day 20 (knowing they were
about to enter a longer than usual fast day).
RMR was not significantly changed after 3 wk of alternate-day
fasting. The effects of 36-h fasts on RMR have not been previ-
ously reported. Horton and Hill (29) observed no differences in
metabolic rate (measured for 12 h in a metabolic chamber after a
mixed meal) between overnight or 3-d fasts. We did observe that
subjects oxidized more fat on day 22 as evidenced by a reduction
in RQ from 0.85 to 0.79. However, RQ was not altered on day 21.
This suggests that there were no sustained increases in fat oxi-
dation on fed days. Caution must be exercised when interpreting
this result, because the subjects did not consume standardized
FIGURE 2. Mean (SEM) fasting glucose, fasting insulin, fasting
-hydroxybutyrate (BHBA), and fasting free fatty acids (FFA) at baseline, day 21, and
day 22 in men (n ҃ 8) and women (n ҃ 8).
Significantly different from baseline, P 0.01 [two-factor (time and sex) repeated-measures ANOVA].
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diets and RQ is heavily dependent on fat intake and energy
balance. However, it is more likely that we underestimated fat
oxidation, because the subjects were coming out of positive en-
ergy balance and because overall fat oxidation was increased by
an average of 15 g/d. Furthermore, because weight loss is
positively correlated with increased fat oxidation, the results
suggest that the subjects with a greater ability to oxidize fat lost
more weight. Alternatively, it could be argued that the subjects
who had a greater caloric deficit had increased fat oxidation.
In conclusion, alternate-day fasting is feasible in nonobese
subjects for short time periods, although unlike rodents, the sub-
jects were unable to maintain their body weight. Furthermore, fat
oxidation was increased and translated into fat mass loss. Hunger
on fasting days did not habituate over the course of the study,
which perhaps indicates the unlikelihood of subjects continuing
on this diet for extended periods of time. Whether alternate-day
fasting would promote weight loss in an obese population is
We acknowledge the clinical research staff for their assistance in perform-
ing this study and Julia Volaufova for assistance with the statistical analysis.
LKH, SRS, and ER were involved in developing the study protocol and the
experimental design. CKM and SA administered and analyzed the VAS and
psychological questionnaires. LKH wrote the draft manuscript with contri-
butions from ER, SRS, and CKM. None of the authors had any financial
interests in organizations sponsoring this research.
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... Több vizsgálat eredményei szerint a váltakozó napi böjti étrendek alkalmazása jelentős súlycsökkenést eredményez [27,28]. Egy randomizált klinikai vizsgálatban egészséges önkénteseknél az egy évig tartó kalóriakorlátozó étrend alkalmazása 10,7%-kal csökkentette a testtömeget és 37%-kal a visceralis zsír értékeit, valamint a testzsírtömeg és a bőr alatti zsír mennyisége is szignifikánsan csökkent a kiindulási értékekhez képest. ...
... napon 12 órát, míg a 22. napon 36 órát böjtöltek a résztvevők, és kezdeti testtömegük 2,5 ± 0,5%-át, míg kezdeti zsírtömegük 4 ± 1%-át veszítették el a vizsgálat időtartama alatt, ami szignifikáns csökkenésnek bizonyult. A nemek között nem tapasztaltak jelentős eltérést a testtömeg-és testzsírváltozások mértéke között [28]. ...
... Furthermore, ADF also did not have the burden of chronic poor feeding and other adverse outcomes compared to CR (58). However, some investigators believed that ADF might not be a viable public health intervention because of considerably and continuously reported hunger by Patterson et al. (8,64). It was believed that hunger affected participants' enthusiasm and adherence to fasting (64). ...
... However, some investigators believed that ADF might not be a viable public health intervention because of considerably and continuously reported hunger by Patterson et al. (8,64). It was believed that hunger affected participants' enthusiasm and adherence to fasting (64). In addition, compared to ADF, weekly TRF exerted significant advantages on the regulation of WC, FM, and DBP. ...
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Background The popularity of applying intermittent fasting (IF) has increased as more and more people are trying to avoid or alleviate obesity and metabolic disease. This study aimed to systematically explore the effects of various IF in humans. Methods The randomized controlled trials (RCTs) related to IF vs. non-intervention diet or caloric restriction (CR) were retrieved in PubMed, Web of Science, Cochrane Library database, and Embase. Extraction outcomes included, but were not limited to, weight, body mass index (BMI), waist circumference (WC), fasting glucose, and triglyceride (TG). Results This study includes 43 RCTs with 2,483 participants. The intervention time was at least 1 month, and the median intervention time was 3 months. Contrasting results between IF and non-intervention diet showed that participants had lower weight (weighted mean difference (WMD) = 1.10, 95% CI: 0.09–2.12, p = 0.03) and BMI after IF (WMD = 0.38, 95% CI: 0.08–0.68, p = 0.01). The WC of participants after IF decreased significantly compared with the non-intervention diet (WMD = 1.02, 95% CI: 0.06–1.99, p = 0.04). IF regulated fat mass (FM) more effectively than non-intervention diet (WMD = 0.74, 95% CI: 0.17–1.31, p = 0.01). The fat-free mass of people after IF was higher (WMD = −0.73, 95% CI: (−1.45)–(−0.02), p = 0.05). There was no difference in fasting blood glucose concentrations between participants in the after IF and non-intervention diet groups. The results of insulin concentrations and HOMA-IR, though, indicated that IF was significantly more beneficial than non-intervention diet (standard mean difference (SMD) = −0.21, 95% CI: 0.02–0.40, p = 0.03, and WMD = 0.35, 95% CI: 0.04–0.65, p = 0.03, respectively). Cholesterol and TG concentrations in participants after IF were also lower than that after a nonintervention diet (SMD = 0.22, 95% CI: 0.09–0.35, p = 0.001 and SMD = 0.13, 95% CI: 0.00–0.26, p = 0.05, respectively). IF outcomes did not differ from CR except for reduced WC. Conclusion Intermittent fasting was more beneficial in reducing body weight, WC, and FM without affecting lean mass compared to the non-intervention diet. IF also effectively improved insulin resistance and blood lipid conditions compared with non-intervention diets. However, IF showed less benefit over CR.
... Fortunately, this ethical and experimental limitation has motivated the search for sustainable approaches to extend health-span beyond their exclusive application on traditional classic animal models like Nematode whereas studies have shown that the reduction of their food source can effectively extend their lifespan as the restriction increases to starvation (Wei et al., 2008, p. 9), similar to the mammalian model system. Alternate healthy feeding strategies, including the in vogue intermittent fasting which involves alternating intervals of extreme calorie reduction with periods of normal eating (Anson et al., 2003;Heilbronn et al., 2005;Varady et al., 2009) and time-restricted feeding (Chaix et al., 2014) each mimic the effects of CR. Such studies of various types of fasting (less than 24 h) have shown reduced levels of pro-inflammatory cytokines, such as IL-1β, IL-6 or TNF-α (Faris et al., 2012). ...
The human intestinal microbiota is composed of several types of microorganisms, including bacteria, archaea, fungi, unicellular eukaryotes and viruses. Among them, bacteria are the most diverse and abundant with a gene catalog 150 times larger than the genes present in the human genome, which represents a tremendous metabolic potential. These bacteria actively participate in the maintenance of intestinal homeostasis. Dysbiosis of the gut microbiota could be observed at course of many human pathologies, particularly inflammatory diseases intestinal chronic diseases (IBD), such as Crohn's disease (CD) or Ulcerative colitis (UC). These dysbiosis could contribute to the onset and progression of diseases. For example, gut microbiota transplantation experiments in murine model have allowed to show that a dysbiotic microbiota is sufficient to induce chronic inflammation in the colon and thus lead to the development of a metabolic syndrome or colitis. Different intervention strategies, including fecal transplantation, administration of probiotics or even special nutritional diets have been developed to act on the microbial communities of the digestive tract and to restore homeostasis of host tissues. The success of some interventions like Fecal transplantation represent a proof of concept in humans that acting on the composition of the intestinal microbiota is a strong lever to resolve certain physio pathological situations associated with gut microbiota dysbiosis. Diet is another important method for modulating the gut microbiota since it is the most important factor influencing its composition. In fact, the nutrients ingested can act directly on the composition of the microbiota by serving as substrates for microorganisms and indirectly by modulating intestinal homeostasis and components of the immune system associated, themselves contributing to regulate the composition microbiota. It is expected that ingestion of these beneficial microorga nisms can stimulate the immune system, promote intestinal homeostasis and to some extent contribute to the balance of the microbiota intestinal. The use of probiotic microorganisms is found to be very effective in some studies to treat different physiopathological situations (colitis, metabolic syndrome) in laboratory model organisms (rats, mice), however the use of these same probiotics in humans have given relatively disappointing clinical results, with poorly reproducible results across cohorts of patients. Except for the treatment of antibiotic-associated diarrhea. These discrepancies in results between pre-clinical models and clinical trials encourage better characterization of the molecular mechanisms used by probiotics to exert their beneficial effects and especially better understand the relationship of these probiotic microorganisms with the resident microbiota and diet.Among the different rising intervention strategies practiced nowadays in the purpose to shape the microbiota, a growing interest is given to other dietary interventions, like caloric restriction (CR) which has demonstrated several beneficial effects on various physiological systems, including the gastro-intestinal system, by modulating the innate and adaptative immune responses. In fact, emerging evidence suggests that the immune system function might be heavily influenced by the sensing of nutrient, reinforcing the idea that diet can deeply influence the inflammatory responses.
... Fasting is defined as a period of complete caloric cessation, commonly for 12 h or longer, with ad libitum access to water (4). Intermittent fasting promotes weight loss and increases fat oxidation in individuals with obesity and nonobese individuals (5,6). However, the health benefits of intermittent fasting may go beyond weight loss. ...
Evidence suggests that intermittent fasting improves cardiovascular health by reducing arterial blood pressure, but contributing mechanisms are unclear. The purpose of this study was to determine the influence of an acute fast on hemodynamics, muscle sympathetic nerve activity (MSNA), and autonomic control at rest and during an arterial pressure challenge. Twenty-five young normotensive volunteers were tested twice, in the fed and fasted (24 h) states (randomized). 24-h ambulatory blood pressure was measured before an autonomic function test which consisted of a 10-min period of controlled breathing (CB) at 0.25 Hz followed by 3, 15-s Valsalva maneuvers (VM). We recorded the ECG, beat-to-beat arterial pressure, and MSNA throughout the autonomic test. Vagal-cardiac modulation via heart rate variability (HRV) was assessed in both time- and frequency-domains, cardiovagal baroreflex sensitivity (cvBRS) was assessed with linear regression, and stroke volume was estimated from pulse contour. All fed vs. fasted comparisons presented are different at p<.05. Fasting reduced ambulatory mean arterial pressure (81±1 vs. 78±1mmHg) and heart rate (69±2 vs. 65±2bpm). CB revealed enhanced HRV through increased R-R intervals (992±30 vs. 1059±37ms) and normalized high frequency (HFnu) R-R interval spectral power (55±3 vs. 62±3%). Estimated stroke volume was higher after fasting (by 13%) as was cvBRS (20±2 vs. 26±5ms/mmHg) and cvBRS during phase IV of the VM (9±1 vs 12±1ms/mmHg). MSNA (n=12) did not change (16±11 vs. 15±8 bursts/min; p=.18). Our results show that acute fasting is consistent with improved cardiovascular health: such improvements are driven by reduced ambulatory arterial pressure and enhanced vagal-cardiac modulation.
... It is well-known that most physiological and metabolic functions, including skeletal muscle strength, the energy balance of body organs, and physical and cardiovascular activity gradually worsen with aging [5,18,19]. Experimental evidence suggests that increased with aging oxidative stress underlines most of the above-mentioned deleterious processes [7]. Melatonin is a hormone with powerful antioxidant properties. ...
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The pineal gland is suggested to be an essential area involved in the programming of fertility, growth, aging, and death of mammals via the released hormone melatonin.The present study aimed to ascertain the effect of melatonin deficit on several physiological and metabolic parameters, closely associated with the aging process, at certain stages of ontogenesis. Sham and rats with pinealectomy, operated at ages 3, 14, and 18-months, respectively, were tested two months later. Sham rats demonstrated an age-related decline of muscle strength, exercise endurance, motor activity, food intake, calorimetric parameters, and impaired lipid profile. Pinealectomy reduced the maximal time to exhaustion and body weight gain while diminished motor activity, food intake, O2 consumption, CO2 production, and energy expenditure during the Dark phase in the youngest rat group. In addition, melatonin deficit elevated arterial blood pressure (systolic, diastolic, and mean arterial pressure) and increased serum glucose and triglyceride level in 3-month-old rats while decreased the liver enzyme activity in 14-month-old rats. In conclusion, the present study brought new insights confirming the complex impact of melatonin deficit on important physiological, metabolic and biochemical markers related to aging and demonstrated for the first time that the lack of melatonin hormone is harmful in young adult rats.
Dietary behavior can have a consequential and wide-ranging influence on human health. Intermittent fasting, which involves intermittent restriction in energy intake, has been shown to have beneficial cellular, physiological, and system-wide effects in animal and human studies. Despite the potential utility in preventing, slowing, and reversing disease processes, the clinical application of intermittent fasting remains limited. The health benefits associated with the simple implementation of a 12 to 16 h fast suggest a promising role in the treatment of chronic pain. A literature review was completed to characterize the physiologic benefits of intermittent fasting and to relate the evidence to the mechanisms underlying chronic pain. Research on different fasting regimens is outlined and an overview of research demonstrating the benefits of intermittent fasting across diverse health conditions is provided. Data on the physiologic effects of intermittent fasting are summarized. The physiology of different pain states is reviewed and the possible implications for intermittent fasting in the treatment of chronic pain through non-invasive management, prehabilitation, and rehabilitation following injury and invasive procedures are presented. Evidence indicates the potential utility of intermittent fasting in the comprehensive management of chronic pain and warrants further investigation.
The scientific community currently expresses a high level of interest in intermittent fasting - periods of voluntary abstinence from energy intake, ranging from several hours to days. Intermittent fasting is clinically relevant and may represent an effective non- pharmacological strategy to improve physical performance and body composition. It has been studied mainly in athletes during the religious period of Ramadan and in people predisposed to decrease body fat without loss of fat-free mass parallel. The purpose of this review is to provide an overview of the impact of intermittent fasting during Ramadan vs. non-Ramadan intermittent fasting in terms of physical performance and body composition. The literature shows some inconsistencies in terms of the interaction between intermittent fasting and physical performance. However, non-Ramadan intermittent fasting is found to be effective in improving maximal aerobic power. Nevertheless, this intervention reduces performance during the repeated sprints over the first few days of intervention. On the other hand, intermittent fasting during Ramadan being the maximum aerobic power and this is more expressive during the second half of this religious period. However, both interventions are manifestly innocuous in terms of muscle strength and anaerobic capacity. With regard to body composition, there is greater consensus. According to available data, both interventions encourage beneficial adaptations at this level. Still, fat loss is more pronounced with intermittent non-Ramadan fasting.
Intermittent fasting (IF) has been studied for its effects on lifespan and lifespan as well as the prevention or delay of age-related diseases upon the regulation of metabolic pathways. Mitochondria participate in key metabolic pathways and play important roles in maintaining intracellular signaling networks that modulate various cellular functions. Mitochondrial dysfunction has been described as an early feature of brain aging and neurodegeneration. Although IF has been shown to prevent brain aging and neurodegeneration, the mechanism is still unclear. This review focuses on the mechanisms by which IF improves mitochondrial function, which plays a central role in brain aging and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The cellular and molecular mechanisms of IF in brain aging and neurodegeneration involve activation of adaptive cellular stress responses and signaling- and transcriptional pathways, thereby enhancing mitochondrial function, by promoting energy metabolism and reducing oxidant production.
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The mammary gland is a heterogeneous organ comprising of immune cells, surrounding adipose stromal cells, vascular cells, mammary epithelial, and cancer stem cells. In response to nutritional stimuli, dynamic interactions amongst these cell populations can be modulated, consequently leading to an alteration of the glandular function, physiology, and ultimately disease pathogenesis. For example, obesity, a chronic over-nutritional condition, is known to disrupt homeostasis within the mammary gland and increase risk of breast cancer development. In contrast, emerging evidence has demonstrated that fasting or caloric restriction can negatively impact mammary tumorigenesis. However, how fasting induces phenotypic and functional population differences in the mammary microenvironment is not well understood. In this review, we will provide a detailed overview on the effect of nutritional conditions (i.e., overnutrition or fasting) on the mammary gland microenvironment and its impact on mammary tumor progression.
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Long term chronic calorie restriction (CR) of adult nonhuman primates significantly reduces morbidity and increases median age of death. The present review is focused upon an ongoing study of sustained adult-onset calorie restriction, which has been underway for 15 years. Monkeys, initially calorie restricted at about 10 years of age, are now approximately 25 years old. The median life span of these restricted monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys. In our laboratory, maximum life span for AL-fed monkeys appears to be about 40 years. Thus, whether CR can also increase maximal life span, as it does in rodents, cannot be determined for at least another 15 years. The earliest detectable positive benefit on morbidity in these monkeys was previously reported as the prevention of obesity. Current evidence, as reviewed here, suggests that much obesity-associated morbidity is also mitigated by sustained calorie restraint in nonhuman primates. Furthermore, probably because of the prevention of obesity, diabetes has also been prevented. Recent findings include the identification of extraordinary changes in the glycogen synthesis pathway, and on the phosphorylation of glycogen synthase in response to insulin. This calorie restriction-induced prevention of morbidity does not require excessive leanness, but is clearly present when body fat is within the normal range of 10 to 22%, and this is likely to be true in humans as well.
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Few dietary components are surrounded by more misinformation and myths than the calorie. This confusion can be attributed in part to a lack of accurate and practical methods for assessing energy intake and thus requirements in humans over periods extending beyond several days. The availability of modern respiratory-chamber indirect calorimetry systems and results from human studies with doubly labeled water are now helping to clarify uncertainties surrounding energy requirements. We describe studies of patients with endogenous obesity as an example of how these research methods are resolving long-standing questions regarding energy requirements. The results of these investigations reveal some of the flaws in estimating energy requirements by self-report methods. Advances in accurately measuring energy expenditure are making important contributions to the study of human energy requirements and are providing new and important research opportunities.
We have monitored global changes in gene expression in mouse liver in response to fasting and sugar-fed conditions using high-density microarrays. From approximately 20,000 different genes, the significantly regulated ones were grouped into specific signaling and metabolic pathways. Striking changes in lipid signaling cascade, insulin and dehydroepiandrosterone (DHEA) hormonal pathways, urea cycle and S-adenosylmethionine-based methyl transfer systems, and cell apoptosis regulators were observed. Since these pathways have been implicated to play a role in the aging process, and since we observe significant overlap of genes regulated upon starvation with those regulated upon caloric restriction, our analysis suggests that starvation may elicit a stress response that is also elicited during caloric restriction. Therefore, many of the signaling and metabolic components regulated during fasting may be the same as those which mediate caloric restriction-dependent life-span extension.
Juvenile (1 yr) and adult (3-5 yr) male rhesus monkeys (Macaca mulatta) and juvenile (1-4 yr) and adult (5-10 yr) male squirrel monkeys (Saimiri sciureus) were fed a diet at or near ad libitum levels based on recommended caloric intake for age and body weight or fed 30% less of the same diet with this restriction gradually introduced over a 3-mo period. Analysis of body weights among these respective control and experimental groups from the first year of the study indicated that the monkeys undergoing dietary restriction were gaining weight at a markedly slower rate compared to control values. Actual food intake among diet-restricted groups had been reduced 22-24% below control levels. Periodic analysis of hematology and blood chemistry measurements over the first year of the study detected few significant differences between control and experimental groups to indicate that diet restriction was not detrimental to general health. When values obtained from hematology and blood chemistry measurements of juvenile and adult groups (control and experimental groups combined) were compared to ad libitum fed old monkeys from each species (greater than 18 yr for rhesus; greater than 10 yr for squirrel monkeys), many significant age differences were noted. Among the largest and most consistent findings in both species were age-related decreases in concentrations of lymphocytes, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and phosphates as well as the albumin/globulin ratio and the blood urea nitrogen/creatinine ratio. Age-related increases in serum globulin and creatinine concentrations were also found. These parameters as well as many others being implemented in the study will be monitored further to determine if diet restriction affects the rate of development as well as aging as observed in numerous rodent studies applying such nutritional manipulations.
Beginning at either 1.5, 6 or 10 months of age, male mice from the A/J and C57BL/6J strains and their F1 hybrid, B6AF1/J were fed a diet (4.2 kcal/g) either ad libitum every day or in a restricted fashion by ad libitum feeding every other day. Relative to estimates for ad libitum controls, the body weights of the intermittently-fed restricted C57BL/6J and hybrid mice were reduced and mean and maximum life span were incremented when the every-other-day regimen was initiated at 1.5 or 6 months of age. When every-other-day feeding was introduced at 10 months of age, again both these genotypes lost body weight relative to controls; however, mean life span was not significantly affected although maximum life span was increased. Among A/J mice, intermittent feeding did not reduce body weight relative to ad libitum controls when introduced at 1.5 or 10 months of age; however, this treatment did increase mean and maximum life span when begun at 1.5 months, while it decreased mean and maximum life span when begun at 10 months. When restricted feeding was introduced to this genotype at 6 months of age, body weight reduction compared to control values was apparent at some ages, but the treatment had no significant effects on mean or maximum life span. These results illustrate that the effects of particular regimens of dietary restriction on body weight and life span are greatly dependent upon the genotype and age of initiation. Moreover, when examining the relationship of body weight to life span both between and within the various groups, it was clear that the complexity of this relationship made it difficult to predict that lower body weight would induce life span increment.
This study compared reports of appetite and symptoms in 28 obese subjects randomly assigned to either a 500 calorie protein-sparing modified fast (PSMF) or a 1200-kcal balanced diet. During the first comparison month, subjects consuming the PSMF lost significantly more weight and reported significantly less hunger than did subjects consuming the 1200 kcal diet. Similar results were obtained for the second month, but differences in hunger were not statistically significant. There were no significant differences between conditions in subjects' ratings of their preoccupation with eating or in their ratings of the acceptability or disruptiveness of their diets. PSMF subjects reported significantly greater problems with cold intolerance, constipation, dizziness, dry skin, and fatigue. These symptoms remitted completely, however, when PSMF subjects consumed a 1200-kcal balanced diet. There were no significant differences between conditions in subjects' reports of psychological functioning. Results are discussed in terms of the need for further research to identify the characteristics of PSMF which confer anorexia.
Development of the doubly-labeled water method has made it possible to test the validity of dietary intake instruments for the measurement of energy intake. Comparisons of measured energy expenditure with energy intake from either weighed or estimated dietary records against energy expenditure have indicated that obese subjects, female endurance athletes, and adolescents underestimate habitual and actual energy intake. Individual underestimates of 50% are not uncommon. Even in non-obese adults, where bias is minimal, the standard deviation for individual errors in energy intake approaches 20%. Two investigations of the validity of self-reported dietary records for measuring change in dietary intake also indicate large underestimates of the actual change. Because of bias and imprecision, self-reported energy intakes should be interpreted with caution unless independent methods of assessing their validity are included in the experimental design.