AHS13 Jeffrey Rothschild — Time-restricted Feeding, an Overview of the Current Research and Practical Applications
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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
- 11. Circadian rhythms • External LD cycles cue the suprachiasmatic nucleus (SCN) Schibler et al 2003
- 12. Circadian rhythms • External LD cycles cue the suprachiasmatic nucleus (SCN) • ‘Master clock’ Schibler et al 2003
- 13. Circadian rhythms • Feeding cycles do not affect the SCN • They can independently entrain circadian clocks in peripheral organs
- 14. Discordance…..
- 15. Time-restricted feeding windows • Increasingly practiced • Research has yet to be summarized
- 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.
- 17. Methods • Daily TRF windows of 3-12 h
- 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
- 21. Animal research
- 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
- 33. 12 h TRF window
- 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
- 37. 12 h TRF window - glucose Farooq et al 2006
- 38. 12 h TRF window - cholesterol Farooq et al 2006
- 39. Summary of animal findings
- 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
- 44. Human Research
- 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
- 49. Human Research – Ramadan
- 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
- 52. Ramadan – blood lipids !"#"$"%&" '()*+%,"( -) '()*+%,"( ./. '()*+%,"( 0/. '()*+%,"( -1 23456%7("8(+4(9::; <=' <9>' 9?' <@A' B+C*$D+3"*("8(+4(>AA@ <>?'(EFGH( <>:'(EIG( <@;' >9'(EFGH( @9'(EIG <@;'(EFGH( <9:'(EIG J"K+8L("8(+4(>A9> <M' <9>' 99' <9:' -"K7D*+%("8(+4(>AAA <='(EFGH( <9A'(EIG <99'(EFGH( <9>'(EIG @'(EFGH(( >'(EIG <9:(EFGH( <>:'(EIG N+$"("8(+4(>A99 <O' <:' 9M' <?' 2CP6%,+$("8(+4(>AA; J) J) J) J) !+Q+%P*+3("8(+4(9::: J) J) N7+""("8(+4(>AAO J) ?' <:' J)
- 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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
- 54. Ramadan – blood lipids • Nematy et al used the Framingham risk score to show a significant improvement (p < 0.001) in 10 years coronary heart disease risk !"#"$"%&" '()*+%,"( -. '()*+%,"( /) '()*+%,"( 010 '()*+%,"( 210 '()*+%,"( /3 !"#$%&'()*(+#(,--. /01 /21 /,31 ,41 /051 6+789:+")8()*(+#(3550 /,;21<=>?(@A(<B> /30;C1(<=>?( /3-;,1(<B>( /0.1 3,;,1(<=>?( 05;21(<B> /0.;01(<=>?(/,-;,1( <B> 4"5+67("6(+8(9:;9 <9' <=' <;;' ;;' <;>' D)E':8+&()*(+#(3555 (/C1(<=>?(@A(<B> /.;F1(<=>?(/,5;51( <B> /,,;5(<=>?(/,3;,1( <B> 3;F1(<=>?(3;51( <B> /,-;,(<=>?(/32;.1( <B> G+9)()*(+#(35,, /F1 /-1 ,C1 /41 !7H%&I+9()*(+#(355. @A @A @A @A J+K+&H8+"()*(+#(,--- @A @A @A G'+))()*(+#(355F /31 @A 41 /-1 @A
- 55. Ramadan – blood lipids • Ziaee et al - LDL, HDL and Ø in TC and TG. • TG in overweight and in normal-weight subjects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
- 56. Factors to consider with Ramadan studies….
- 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
- 64. Ramadan – fasting blood glucose !"#"$"%&" '()*+%,"(-.//0(1.2&/3" 40./2%5("6(+.(7889 :7;' <+=*$>+0"*("6(+.(?@@A :A7'(BCDE(:?9'(BFD !+G+%3*+0("6(+.(7888 :?9' H5+""("6(+.(?@@I :7@' J"K+6L("6(+.(?@7? J) M"K5>*+%("6(+.(?@@@ 7N'(BCDE(??'(BFD
- 65. Ramadan – inflammation • IL-6 decreased by 55% • hsCRP decreased 52% Aksungar et al 2007
- 66. Intervention Body weight Lipids Glucose 4 h TRF 8-9 h TRF 10-12 h TRF -- -- ↑, Ø Insulin sensitivity Ø to -5% ↓ TC, ↓ LDL, ↑ HDL, ↓ TG ↓ ↑ FBG -2 to -3% ↓ TC, ↓ LDL, ↑ HDL, ↓ TG ↓ FBG Summary of human findings
- 67. Intervention Body weight Lipids Glucose 4 h TRF 8-9 h TRF 10-12 h TRF -- -- ↑, Ø Insulin sensitivity Ø to -5% ↓ TC, ↓ LDL, ↑ HDL, ↓ TG ↓ ↑ FBG -2 to -3% ↓ TC, ↓ LDL, ↑ HDL, ↓ TG ↓ FBG Summary of human findings
- 68. Conclusion • Eating patterns effect circadian rhythms
- 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
- 70. Practical application • 12-15 h daily fasting window • Can depend on the season
- 71. Don’t eat when it’s dark outside
- 72. Unrestricted food intake internal discordance
- 73. Time-restricted feeding internal harmony
- 74. Thank You • AHS, Dr Varady, Dr Jambazian, Dr Omary, Cal State LA, UIC
- 75. Questions
Editor's Notes
- 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.