Time-restricted feeding is a method of intermittent fasting which allows ad libitum energy intake within a window of 4-12 hours, inducing a 12-20h daily fasted window. A wide variety of health benefits have been seen in animal and human trials, this presentation will review the current research and suggest practical applications.
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AHS13 Jeffrey Rothschild — Time-restricted Feeding, an Overview of the Current Research and Practical Applications
1. TIME-RESTRICTED FEEDING: AN
OVERVIEW OF THE CURRENT RESEARCH
AND PRACTICALAPPLICATIONS
Jeff Rothschild, CSCS, M.S. cand.
Krista Varady, PhD
Pera Jambazian, PhD
2. About Me
• Currently finishing M.S. in Nutritional Science at CSULA
• Coach College tennis
• Work with personal training clients
3. Background
Unrestricted kcal intake
24 h unrestricted
kcal
3-12 h
feeding
12-21 h
fasting
24 h fast
3-12 h
feeding
12-21 h
fasting
Typicaldiet
• 2/3 of U.S. population overweight or obese
• 1/3 of U.S. adults meet criteria for metabolic synd
4. Intermittent Fasting
48 h unrestricted kcal intake
24 h
unrestricted kcal
3-12 h
feeding
12-21 h
fasting
24 h fast
(or ~500 kcal)
3-12 h
feeding
12-21 h
fasting
NormaldietADF/ADMF
• weight loss
• LDL-C, trigs, BP and visceral fat mass
• insulin sensitivity
5. Time-Restricted Feeding
48 h unrestricted kcal intake
24 h unrestricted
kcal
3-12 h
feeding
12-21 h
fasting
24 h fast
3-12 h
feeding
12-21 h
fasting
ADF/ADMFTRFNormaldiet
6. Circadian rhythms
• Bio-rhythms in the absence of external time cues for ~24h
• Reset from environmental changes (light-dark,
temperature and feeding cycles)
7. Circadian rhythms
• Affect food metabolism and energy balance
greater impairment of glucose tolerance than the
global knockout, as predicted. Islets from both
global and pancreas-specific knockouts have
normal insulin content, and influx of calcium in
response to glucose is intact. However, exocytosis
is impaired, suggesting that the clock controls the
latest stage in stimulus-secretion coupling.
Findings in experimental genetic models of
clock-gene ablation may also have implications
for understanding emerging evidence that the
circadian system participates in human glucose
metabolism. For instance, in genome-wide associa-
tion studies, variation in the Melatonin 1b receptor
(MTNR1B) and in Cry2 are both associated with
blood glucose concentrations
[(52) and reviewed in (53)].
MTNR1B, the cognate receptor
of the circadian-regulated hor-
mone melatonin, is expressed
in many metabolic tissues,
whereas Cry2 encodes a clock
repressor. These findings un-
derscore the need to incorpo-
rate temporal considerations
at the planning stages in future
studies to account for circadian
variation. Similarly, temporal
considerations may aid in anal-
ysis of experimental genetic
models because testing at dif-
ferent times and under different
environmental light cycles may
uncover unanticipated effects.
Sleep and forced circadian
misalignment: genetic models
and human studies. Ties be-
tween circadian disruption and
metabolic disturbance have
garnered attention, including
large cross-sectional sampling
of populations subjected to
shift work. Extensive studies
also indicate a correlation be-
tween sleep time and body
mass index (BMI). Disruption
in specific phases of sleep may
be connected to metabolic func-
tion. Subtle tones sufficient to
selectively deprive subjects of
indicates that lack of orexin signaling increases
susceptibility to obesity (rather than the original
expectation that orexin, a potent wakefulness-
inducing peptide, would induce adiposity) (57).
Orexin receptor 2 mutations also account for
canine narcolepsy, and orexin deficiency is a
hallmark of the disease in humans (58). Activity
of the orexin neuron is modulated by glucose and
integrates signals downstream of leptin-responsive
neurons within the arcuate nucleus. Leptin also
affects sleep, possibly independently of effects
on body weight, raising the need to further define
leptin actions in this process (59). Manipulation
of orexin signaling, an integrator of energetic and
pulation that is intended to simulate deleterious
effects of jet lag or shift work, caused impaired
glucose tolerance and hypoleptinemia. Whether
circadian disruption might also affect endocrine
pancreas insulin secretion, hepatic gluconeogenesis,
and glucose disposal in skeletal muscle in humans
awaits further study; however, these results empha-
size the clinical linkages between circadian function
and metabolic homeostasis.
Coupling and Outputs: How Do Clocks Sense
and Respond to Nutrient Signals?
Under homeostatic conditions, the clock acts as a
driver of metabolic physiology (Fig. 3). However,
Sleep deprivation
Prolonged wakefulness
High-fat diet
Pancreas
Insulin secretion
Fat
Lipogenesis
Adiponectin production
Muscle
Fatty acid uptake
Glycolytic metabolism
Liver
Glycogen synthesis
Cholesterol synthesis
Bile acid synthesis
SLEEP
FASTING
Insulin
s
ecretion
SympathetictoneGlucocorticoids
Growth hormone
Melatoninsecretion
Insulin resistance
Insulin s
ecretion
WAKE
FEEDING
Leptin secretion
Gluconeoge
nesis
Liver
Gluconeogenesis
Glycogenolysis
Mitochondrial biogenesis
Muscle
Oxidative metabolism
Pancreas
Glucagon secretion
Fat
Lipid catabolism
Leptin secretion
Fig. 3. The clock partitions behavioral and metabolic processes according to time of day. The clock coordinates ap-
propriate metabolic responses within peripheral tissues with the light/dark cycle. For example, the liver clock promotes
gluconeogenesis and glycogenolysis during the sleep/fasting period, whereas it promotes glycogen and cholesterol
synthesis during the wake/feeding period. Proper functioning of peripheral clocks keeps metabolic processes in synchrony
SPECIALSECTION
onDecember2,2010www.sciencemag.orgDownloadedfrom
Bass and Takahashi 2010
8. Circadian rhythms
Bass and Takahashi 2010
e to glucose is intact. However, exocytosis
red, suggesting that the clock controls the
age in stimulus-secretion coupling.
dings in experimental genetic models of
ene ablation may also have implications
derstanding emerging evidence that the
n system participates in human glucose
ism. For instance, in genome-wide associa-
dies, variation in the Melatonin 1b receptor
1B) and in Cry2 are both associated with
glucose concentrations
nd reviewed in (53)].
1B, the cognate receptor
circadian-regulated hor-
melatonin, is expressed
ny metabolic tissues,
s Cry2 encodes a clock
or. These findings un-
e the need to incorpo-
mporal considerations
lanning stages in future
to account for circadian
n. Similarly, temporal
rations may aid in anal-
experimental genetic
because testing at dif-
mes and under different
mental light cycles may
unanticipated effects.
p and forced circadian
nment: genetic models
man studies. Ties be-
ircadian disruption and
lic disturbance have
d attention, including
oss-sectional sampling
ulations subjected to
ork. Extensive studies
dicate a correlation be-
sleep time and body
dex (BMI). Disruption
fic phases of sleep may
ected to metabolic func-
Orexin receptor 2 mutations also account for
canine narcolepsy, and orexin deficiency is a
hallmark of the disease in humans (58). Activity
of the orexin neuron is modulated by glucose and
integrates signals downstream of leptin-responsive
neurons within the arcuate nucleus. Leptin also
affects sleep, possibly independently of effects
on body weight, raising the need to further define
leptin actions in this process (59). Manipulation
of orexin signaling, an integrator of energetic and
pancreas insulin secretion, hepatic gluconeogenesis,
and glucose disposal in skeletal muscle in humans
awaits further study; however, these results empha-
size the clinical linkages between circadian function
and metabolic homeostasis.
Coupling and Outputs: How Do Clocks Sense
and Respond to Nutrient Signals?
Under homeostatic conditions, the clock acts as a
driver of metabolic physiology (Fig. 3). However,
Sleep deprivation
Prolonged wakefulness
High-fat diet
Pancreas
Insulin secretion
Fat
Lipogenesis
Adiponectin production
Muscle
Fatty acid uptake
Glycolytic metabolism
Liver
Glycogen synthesis
Cholesterol synthesis
Bile acid synthesis
SLEEP
FASTING
Insulin
s
ecretion
SympathetictoneGlucocorticoids
Growth hormone
Melatoninsecretion
Insulin resistance
Insulin s
ecretion
WAKE
FEEDING
Leptin secretion
Gluconeogenesis
Liver
Gluconeogenesis
Glycogenolysis
Mitochondrial biogenesis
Muscle
Oxidative metabolism
Pancreas
Glucagon secretion
Fat
Lipid catabolism
Leptin secretion
Fig. 3. The clock partitions behavioral and metabolic processes according to time of day. The clock coordinates ap-
propriate metabolic responses within peripheral tissues with the light/dark cycle. For example, the liver clock promotes
onDecember2,2010www.sciencemag.orgDownloadedfrom
9. e to glucose is intact. However, exocytosis
red, suggesting that the clock controls the
age in stimulus-secretion coupling.
dings in experimental genetic models of
ene ablation may also have implications
derstanding emerging evidence that the
n system participates in human glucose
ism. For instance, in genome-wide associa-
dies, variation in the Melatonin 1b receptor
1B) and in Cry2 are both associated with
glucose concentrations
nd reviewed in (53)].
1B, the cognate receptor
circadian-regulated hor-
melatonin, is expressed
ny metabolic tissues,
s Cry2 encodes a clock
or. These findings un-
e the need to incorpo-
mporal considerations
lanning stages in future
to account for circadian
n. Similarly, temporal
rations may aid in anal-
experimental genetic
because testing at dif-
mes and under different
mental light cycles may
unanticipated effects.
p and forced circadian
nment: genetic models
man studies. Ties be-
ircadian disruption and
lic disturbance have
d attention, including
oss-sectional sampling
ulations subjected to
ork. Extensive studies
dicate a correlation be-
sleep time and body
dex (BMI). Disruption
fic phases of sleep may
ected to metabolic func-
Orexin receptor 2 mutations also account for
canine narcolepsy, and orexin deficiency is a
hallmark of the disease in humans (58). Activity
of the orexin neuron is modulated by glucose and
integrates signals downstream of leptin-responsive
neurons within the arcuate nucleus. Leptin also
affects sleep, possibly independently of effects
on body weight, raising the need to further define
leptin actions in this process (59). Manipulation
of orexin signaling, an integrator of energetic and
pancreas insulin secretion, hepatic gluconeogenesis,
and glucose disposal in skeletal muscle in humans
awaits further study; however, these results empha-
size the clinical linkages between circadian function
and metabolic homeostasis.
Coupling and Outputs: How Do Clocks Sense
and Respond to Nutrient Signals?
Under homeostatic conditions, the clock acts as a
driver of metabolic physiology (Fig. 3). However,
Sleep deprivation
Prolonged wakefulness
High-fat diet
Pancreas
Insulin secretion
Fat
Lipogenesis
Adiponectin production
Muscle
Fatty acid uptake
Glycolytic metabolism
Liver
Glycogen synthesis
Cholesterol synthesis
Bile acid synthesis
SLEEP
FASTING
Insulin
s
ecretion
SympathetictoneGlucocorticoids
Growth hormone
Melatoninsecretion
Insulin resistance
Insulin s
ecretion
WAKE
FEEDING
Leptin secretion
Gluconeogenesis
Liver
Gluconeogenesis
Glycogenolysis
Mitochondrial biogenesis
Muscle
Oxidative metabolism
Pancreas
Glucagon secretion
Fat
Lipid catabolism
Leptin secretion
Fig. 3. The clock partitions behavioral and metabolic processes according to time of day. The clock coordinates ap-
propriate metabolic responses within peripheral tissues with the light/dark cycle. For example, the liver clock promotes
onDecember2,2010www.sciencemag.orgDownloadedfrom
Circadian rhythms
10. e to glucose is intact. However, exocytosis
red, suggesting that the clock controls the
age in stimulus-secretion coupling.
dings in experimental genetic models of
ene ablation may also have implications
derstanding emerging evidence that the
n system participates in human glucose
ism. For instance, in genome-wide associa-
dies, variation in the Melatonin 1b receptor
1B) and in Cry2 are both associated with
glucose concentrations
nd reviewed in (53)].
1B, the cognate receptor
circadian-regulated hor-
melatonin, is expressed
ny metabolic tissues,
s Cry2 encodes a clock
or. These findings un-
e the need to incorpo-
mporal considerations
lanning stages in future
to account for circadian
n. Similarly, temporal
rations may aid in anal-
experimental genetic
because testing at dif-
mes and under different
mental light cycles may
unanticipated effects.
p and forced circadian
nment: genetic models
man studies. Ties be-
ircadian disruption and
lic disturbance have
d attention, including
oss-sectional sampling
ulations subjected to
ork. Extensive studies
dicate a correlation be-
sleep time and body
dex (BMI). Disruption
fic phases of sleep may
ected to metabolic func-
Orexin receptor 2 mutations also account for
canine narcolepsy, and orexin deficiency is a
hallmark of the disease in humans (58). Activity
of the orexin neuron is modulated by glucose and
integrates signals downstream of leptin-responsive
neurons within the arcuate nucleus. Leptin also
affects sleep, possibly independently of effects
on body weight, raising the need to further define
leptin actions in this process (59). Manipulation
of orexin signaling, an integrator of energetic and
pancreas insulin secretion, hepatic gluconeogenesis,
and glucose disposal in skeletal muscle in humans
awaits further study; however, these results empha-
size the clinical linkages between circadian function
and metabolic homeostasis.
Coupling and Outputs: How Do Clocks Sense
and Respond to Nutrient Signals?
Under homeostatic conditions, the clock acts as a
driver of metabolic physiology (Fig. 3). However,
Sleep deprivation
Prolonged wakefulness
High-fat diet
Pancreas
Insulin secretion
Fat
Lipogenesis
Adiponectin production
Muscle
Fatty acid uptake
Glycolytic metabolism
Liver
Glycogen synthesis
Cholesterol synthesis
Bile acid synthesis
SLEEP
FASTING
Insulin
s
ecretion
SympathetictoneGlucocorticoids
Growth hormone
Melatoninsecretion
Insulin resistance
Insulin s
ecretion
WAKE
FEEDING
Leptin secretion
Gluconeogenesis
Liver
Gluconeogenesis
Glycogenolysis
Mitochondrial biogenesis
Muscle
Oxidative metabolism
Pancreas
Glucagon secretion
Fat
Lipid catabolism
Leptin secretion
Fig. 3. The clock partitions behavioral and metabolic processes according to time of day. The clock coordinates ap-
propriate metabolic responses within peripheral tissues with the light/dark cycle. For example, the liver clock promotes
onDecember2,2010www.sciencemag.orgDownloadedfrom
Circadian rhythms
16. Objective
• To summarize the current literature on the
effects of TRF on body weight and other
markers of metabolic disease risk in animals
and humans.
18. Methods
• Daily TRF windows of 3-12 h
• Primary endpoints of body weight and/or
biomarkers of metabolic disease risk
19. Methods
• Daily TRF windows of 3-12 h
• Primary endpoints of body weight and/or biomarkers of
metabolic disease risk
• A minimum of 14 d following a TRF protocol
20. Methods
• Daily TRF windows of 3-12 h
• Primary endpoints of body weight and/or biomarkers of
metabolic disease risk
• A minimum of 14 d following a TRF protocol
• More than 60 studies on Ramadan were found
• Eight included based on largest sample sizes (n ≥ 32), and
inclusion of four or more relevant parameters
22. Animal research
3-4 h TRF Light phase feeding 16-18 weeks
8-9 h TRF Dark phase feeding 16 weeks
12 h TRF
Light vs dark phase
Low-fat vs high-fat during dark phase
4-6 weeks
16 weeks
23. Animal research
3-4 h TRF Light phase feeding 16-18 weeks
8-9 h TRF Dark phase feeding 16 weeks
12 h TRF
Light vs dark phase
Low-fat vs high-fat during dark phase
4-6 weeks
16 weeks
24. Animal research
3-4 h TRF Light phase feeding 16-18 weeks
8-9 h TRF Dark phase feeding 16 weeks
12 h TRF
Light vs dark phase
Low-fat vs high-fat during dark phase
4-6 weeks
16 weeks
• Mice normally consume
60-80% of their daily caloric
intake during the dark-phase
25. 3-4 h TRF window – weight gain
• Body weights were 17-18% lower
• Body weight of mice on TRF-HFD
was 12% lower than AL-LFD in
spite of the same energy intake
Sherman et al 2012
26. 3-4 h TRF window
Sherman et al 2011, 2012
• Two studies showing decreases in
triglycerides, total cholesterol,
TNF-α, IL-6 and NF-kb
• Increased insulin sensitivity
TNF-αIL-6
27. 8 h TRF window
• Fed mice a high-fat or normal diet during dark hrs,
16 weeks
• Is a calorie always a calorie???
• In the context of circadian biology, maybe not
NA = normal chow (13% fat) ad lib
NT = normal chow 8 h TRF
FA = high fat (61% fat) ad lib
FT = high fat 8 h TRF
Hatori et al 2012
28. 8 h TRF window
• Differences in body weight
• TRF-HFD consumed = kcals as AL-HFD but weighed 28% less
• TRF normal diet weighed less than AL though the difference did not
reach statistical significance
NA = normal chow (13% fat) ad lib
NT = normal chow 8 h TRF
FA = high fat (61% fat) ad lib
FT = high fat 8 h TRF
Hatori et al 2012
29. 8 h TRF window
• Differences in body weight
• TRF-HFD consumed = kcals as AL-HFD but weighed 28% less
• TRF normal diet weighed less than AL though the difference did not
reach statistical significance
NA = normal chow (13% fat) ad lib
NT = normal chow 8 h TRF
FA = high fat (61% fat) ad lib
FT = high fat 8 h TRF
Hatori et al 2012
30. 8 h TRF window
• Total cholesterol
• 49% decrease in TC in mice on
TRF-HFD
Hatori et al 2012
31. 8 h TRF window
• Glucose tolerance
• Comparable to the controls
Hatori et al 2012
32. 8 h TRF window
• Inflammatory markers
• Decreased TNF-α both groups
Hatori et al 2012
34. 12 h TRF window – body weight
• Fed mice during 12 h light or dark phase, 5 weeks
• Kcals and activity were not different
• Dark-phase fed weighed 13% less than light-phase fed
• Less visceral fat
Salgado-Delgado et al 2010
35. 12 h TRF window – body weight
• Fed mice during 12 h light or dark phase, 6 weeks
• Kcals and activity were not different
• Dark-phase fed weighed 19% less than light-phase fed
Arble et al 2009
36. 12 h TRF window – body weight
• Mice fed a low-fat and high-fat diet during the 12 h dark-
phase only, 16 weeks
• No differences in kcals or activity
• TRF showed decreased weight gain, independent of the diet
Tsai et al 2012
40. Summary of animal findings
Intervention Body weight Lipids Glucose Inflammation
3-4 h TRF
8-9 h TRF
12 h TRF
-9 to -18%
↓ TC, ↓ LDL,
↓ HDL, ↓ TG
↓ Insulin
resistance
↓ Il-6, ↓ TNF-a,
↓ CRP, ↓ NFkb
Ø to -28% ↓ TC
↑ Insulin
sensitivity
↓ Il-6, ↓ TNF-a
Ø to -19% ↓ TC, ↓ TG ↓ Glucose --
41. Summary of animal findings
Intervention Body weight Lipids Glucose Inflammation
3-4 h TRF
8-9 h TRF
12 h TRF
-9 to -18%
↓ TC, ↓ LDL,
↓ HDL, ↓ TG
↓ Insulin
resistance
↓ Il-6, ↓ TNF-a,
↓ CRP, ↓ NFkb
Ø to -28% ↓ TC
↑ Insulin
sensitivity
↓ Il-6, ↓ TNF-a
Ø to -19% ↓ TC, ↓ TG ↓ Glucose --
42. Summary of animal findings
Intervention Body weight Lipids Glucose Inflammation
3-4 h TRF
8-9 h TRF
12 h TRF
-9 to -18%
↓ TC, ↓ LDL,
↓ HDL, ↓ TG
↓ Insulin
resistance
↓ Il-6, ↓ TNF-a,
↓ CRP, ↓ NFkb
Ø to -28% ↓ TC
↑ Insulin
sensitivity
↓ Il-6, ↓ TNF-a
Ø to -19% ↓ TC, ↓ TG ↓ Glucose --
43. Summary of animal findings
Intervention Body weight Lipids Glucose Inflammation
3-4 h TRF
8-9 h TRF
12 h TRF
-9 to -18%
↓ TC, ↓ LDL,
↓ HDL, ↓ TG
↓ Insulin
resistance
↓ Il-6, ↓ TNF-a,
↓ CRP, ↓ NFkb
Ø to -28% ↓ TC
↑ Insulin
sensitivity
↓ Il-6, ↓ TNF-a
Ø to -19% ↓ TC, ↓ TG ↓ Glucose --
Eating at the physiologically ‘wrong’ time can lead to
increased weight gain, visceral fat, blood lipids and
inflammation along with decreased glycemic control
45. 4 h TRF window
• 4h TRF every other day for 15 days in healthy men
• Subjects were instructed to eat enough to maintain body weight
Halberg et al 2005
46. 4 h TRF window
• 4h TRF every other day for 15 days in healthy men
• Subjects were instructed to eat enough to maintain body weight
• Insulin-mediated whole body glucose uptake rates increased 16%
• Insulin-induced inhibition of lipolysis became more prominent
• No changes in IL-6 or TNF-α
Halberg et al 2005
47. 4 h TRF window
• Soeters et al 2009 used the same TRF protocol, also
adjusted energy intake to prevent weight change
• No improvements in peripheral or hepatic insulin sensitivity, or any
changes in insulin-induced suppression of lipolysis
48. 4 h TRF window
• Soeters et al 2009 used the same TRF protocol, also
adjusted energy intake to prevent weight change
• However, these participants consumed 40% of their daily energy
intake from liquid meals, which may cause different gastric,
pancreatic, and biliary responses than consumption of solid meals
50. Ramadan – weight change
• Weight changes have ranged from no differences to 5%
weight loss
51. Ramadan – weight change
Reference Weight Change
Adlouni et al 1997
Nematy et al 2012
Ziaee et al 2006
Temizhan et al 2000
Fakhrzadeh et al 2003
Ravanshad et al 1999
-3%
-2%
-2%
-5% Men, NC Women
-1.8% Men, NC Women
NC
53. Ramadan – blood lipids
• Temizhan et al found women had greater improvements in
lipid values than men, but without weight loss
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57. Intake
• Total energy intake may affect blood lipid values
• Research has shown decreases, no changes, or
even increases in energy intake during Ramadan
58. Macros
• There are contrasting reports of whether people
change or do not change their macronutrient
intakes during Ramadan fasting
59. Meal timing
• During Ramadan, people eat during the
physiologically ‘wrong’ time
greater impairment of glucose tolerance than the
global knockout, as predicted. Islets from both
global and pancreas-specific knockouts have
normal insulin content, and influx of calcium in
response to glucose is intact. However, exocytosis
is impaired, suggesting that the clock controls the
latest stage in stimulus-secretion coupling.
Findings in experimental genetic models of
clock-gene ablation may also have implications
for understanding emerging evidence that the
circadian system participates in human glucose
metabolism. For instance, in genome-wide associa-
tion studies, variation in the Melatonin 1b receptor
(MTNR1B) and in Cry2 are both associated with
blood glucose concentrations
[(52) and reviewed in (53)].
MTNR1B, the cognate receptor
of the circadian-regulated hor-
mone melatonin, is expressed
in many metabolic tissues,
whereas Cry2 encodes a clock
repressor. These findings un-
derscore the need to incorpo-
rate temporal considerations
at the planning stages in future
studies to account for circadian
variation. Similarly, temporal
considerations may aid in anal-
ysis of experimental genetic
models because testing at dif-
ferent times and under different
environmental light cycles may
uncover unanticipated effects.
Sleep and forced circadian
misalignment: genetic models
and human studies. Ties be-
tween circadian disruption and
metabolic disturbance have
garnered attention, including
large cross-sectional sampling
of populations subjected to
shift work. Extensive studies
also indicate a correlation be-
tween sleep time and body
mass index (BMI). Disruption
in specific phases of sleep may
be connected to metabolic func-
tion. Subtle tones sufficient to
selectively deprive subjects of
slow-wavesleepwithoutproduc-
indicates that lack of orexin signaling increases
susceptibility to obesity (rather than the original
expectation that orexin, a potent wakefulness-
inducing peptide, would induce adiposity) (57).
Orexin receptor 2 mutations also account for
canine narcolepsy, and orexin deficiency is a
hallmark of the disease in humans (58). Activity
of the orexin neuron is modulated by glucose and
integrates signals downstream of leptin-responsive
neurons within the arcuate nucleus. Leptin also
affects sleep, possibly independently of effects
on body weight, raising the need to further define
leptin actions in this process (59). Manipulation
of orexin signaling, an integrator of energetic and
pulation that is intended to simulate deleterious
effects of jet lag or shift work, caused impaired
glucose tolerance and hypoleptinemia. Whether
circadian disruption might also affect endocrine
pancreas insulin secretion, hepatic gluconeogenesis,
and glucose disposal in skeletal muscle in humans
awaits further study; however, these results empha-
size the clinical linkages between circadian function
and metabolic homeostasis.
Coupling and Outputs: How Do Clocks Sense
and Respond to Nutrient Signals?
Under homeostatic conditions, the clock acts as a
driver of metabolic physiology (Fig. 3). However,
Sleep deprivation
Prolonged wakefulness
High-fat diet
Pancreas
Insulin secretion
Fat
Lipogenesis
Adiponectin production
Muscle
Fatty acid uptake
Glycolytic metabolism
Liver
Glycogen synthesis
Cholesterol synthesis
Bile acid synthesis
SLEEP
FASTING
Insulin
s
ecretion
SympathetictoneGlucocorticoids
Growth hormone
Melatoninsecretion
Insulin resistance
Insulin s
ecretion
WAKE
FEEDING
Leptin secretion
Gluconeoge
nesis
Liver
Gluconeogenesis
Glycogenolysis
Mitochondrial biogenesis
Muscle
Oxidative metabolism
Pancreas
Glucagon secretion
Fat
Lipid catabolism
Leptin secretion
Fig. 3. The clock partitions behavioral and metabolic processes according to time of day. The clock coordinates ap-
propriate metabolic responses within peripheral tissues with the light/dark cycle. For example, the liver clock promotes
gluconeogenesis and glycogenolysis during the sleep/fasting period, whereas it promotes glycogen and cholesterol
synthesis during the wake/feeding period. Proper functioning of peripheral clocks keeps metabolic processes in synchrony
with the environment, which is critical for maintaining health of the organism. Different tissues exhibit distinct clock-
SPECIALSECTION
onDecember2,2010www.sciencemag.orgDownloadedfrom
60. Sleep schedule
• Sleep patterns are drastically changed to allow for
early morning meals, affecting metabolism
61. Seasonality
• Ramadan takes place according to the Islamic calendar,
occurring at a different date each year
• Differences in latitude may lead to fasting times of 8-16 hrs
62. Lab testing
• Some studies have performed blood draws in the
morning while others in the late afternoon,
possibly affecting results
63. And finally…
• Studies that show disparities with trends reviewed
here are few in number and generally have smaller
sample sizes of 8-25 people
• This review included studies with sample sizes of 32-91
people
69. Conclusion
• Findings from animal and human studies suggest
that TRF may be an effective dietary intervention
to improve a variety of metabolic risk factors
• Plasma lipids
• Fasting glucose and insulin
• Insulin sensitivity
• Inflammatory cytokines
Affect food metabolism and energy balance by regulating the activity of enzymes involved in cholesterol, lipid, amino acid, glycogen, and glucose metabolism
External LD cycles cue the suprachiasmatic nucleus (SCN), regarded as the master clock which entrains the circadian oscillations….
External LD cycles cue the suprachiasmatic nucleus (SCN), regarded as the master clock which entrains the circadian oscillations….
The human body is prepared for activity and food ingestion during daylight hours and for rest and fasting during darkness, and eating outside of physiologically 'normal' times may lead to an internal discordance in which food intake shifts the circadian rhythms of peripheral organs while the master clock remains set to the LD cycle.
The human body is prepared for activity and food ingestion during daylight hours and for rest and fasting during darkness, and eating outside of physiologically 'normal' times may lead to an internal discordance in which food intake shifts the circadian rhythms of peripheral organs while the master clock remains set to the LD cycle.
Ramadan
Soeters et al also noted that subjects consumed mainly bread, fruit, and dairy products, while the earlier study simply instructed subjects to consume meals with normal macronutrient mixing and to eat sufficient quantities of food. Both studies adjusted energy intake to prevent weight loss, which would have likely occurred on a 4 h TRF protocol.
Energy intakes must be interpreted with caution however, because the commonly used methods of dietary recall (24h recall, 3-7d food log, FFQ) may not give accurate estimates of energy intakes in individuals though means of group intakes may be considered more accurate. This is further evidenced by these studies reporting daily energy intakes between 1200-2800 kcal/day in normal weight subjects…
Five of the eight studies found favorable changes in TC, HDL, LDL-cholesterol (LDL) and TG levels and thus improvements in TC:HDL ratios, two showed no changes
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
These are but a few of the possible confounding variables to be considered when evaluating the literature on Ramadan, and support the need for further human trials using TRF.
After = 20 days after ramadan
The human body is prepared for activity and food ingestion during daylight hours and for rest and fasting during darkness, and eating outside of physiologically 'normal' times may lead to an internal discordance in which food intake shifts the circadian rhythms of peripheral organs while the master clock remains set to the LD cycle.
The human body is prepared for activity and food ingestion during daylight hours and for rest and fasting during darkness, and eating outside of physiologically 'normal' times may lead to an internal discordance in which food intake shifts the circadian rhythms of peripheral organs while the master clock remains set to the LD cycle.