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Dr. Sudharani, N.
Assistant Professor
(Food Science and Nutrition)
College of Horticulture
Mudigere, Karnataka-577132
One time eater – YoGi
Two time eater – Bhogi
Three time eater – Hothkondogi
Topic division
Introduction
Reviews
Summary
Conclusion
Referenc
es
Diet
Types of fasting(Dietary restriction)
• Calorie Restriction - CR:
Chronic reduction of 20-40% of the caloric intake.
• Prolonged Fasting - PF:
which lasts more than 72 hr (4-7 days).
• Fast Mimicking Diet - FMD:
Prolonged and periodic fasting protocol which does not
consider the whole abstinence from food.
• Intermittent Fasting - IF:
Rizza and Wanna, 2017
Intermittent fasting
• Switching between fasting states and feeding
states (Switch on: Switch off) or (fast: feed).
• This fasting state can last 16 to 48 hrs and IF can
be combined with any dietary protocol.
3 Meals a day with regular snacking
Example of following an IF (TRF) protocol
Fat burning during fastingFatStorageFatburning
Hours since last meal
Insulin Response to Macronutrients
FatStorageFatburning
Hours since last meal
Fat Protein
Fasting
Carbohy
drates
Insulin
Ways to undertake Intermittent fasting
Time restricted eating
Alternative day fasting
Weekly IF
Rizza and Wanna, 2017
How to get started
How to do IF
“One size doesn’t fit all”
Lean gains Daily Intermittent Fasting (TRF)
16–hour fast :
8–hour eating period
Weekly Intermittent Fasting
One 24-hour fast each week
In this example, lunch on Monday is your last
meal of the day.
You then fast until lunch on Tuesday.
Alternate Day Intermittent Fasting
(Warrior diet)
Fast for alternating 24-hour periods (20:4)
 Ori Hofmekler
This style of intermittent fasting is often
used in research studies.
But it is not very popular in the real world.
Benefits of IF
 Loose weight
 Reduces
 CVD
 Diabetes
 Aging process
 Cleans cells & Rejuvenate
 Induce Autophagy
Eating Disorder
Body Dysmorphia
Type 1 Diabetes
Pregnant or Breastfeeding
Medication
Derived from Greek words “auto” meaning self
and “phagy” means eating.
Autophagy is a normal physiological process of
catabolic degradation where protein and organelles
are engulfed into autophagosomes, digested in
lysosomes and recycled to sustain cellular
metabolism during stress.
Survival, Development and Homeostasis
Dr. , Nobel Laureate, 2016
Schematic presentation of Autophagosome formation
Types of AP
• Macro AP
• Micro AP
• Chaperone AP
Growth/ proliferation
Recycle nutrients
Autopahgic cell death
Cellular stress
Starvation
mTOR
Energy
Infection controlProteostasis
Organelle Homeostasis
HEALTH & DISEASE
• mTOR- protein kinase.
• Links and acts as core
component.
• Central regulator of metabolism
and physiology
• Regulates cell growth,
proliferation, motility, survival,
protein synthesis, transcription
and autophagy.
• mTOR inhibition autophagy.
• AMP-activated protein kinase
• master regulator of cellular energy
homeostasis.
• activated in stresses
• During glucose starvation, the ratio of
AMP :ATP increases, leading to the
activation of AMPK.
• AMPK stimulates the autophagy
Regulation of AP
Zhineng et al., 2011 & Eeva et al., 2009
Atg 5-
cardiomyopathy
Xie et al., 2017
Calorie restriction mimetics (CRM)
• Aging
• High carbohydrates
• Frequent meal consumption
• High Insulin
Objective:
Investigate the effect of a modified Intermittent
Fasting protocol (TRF) in healthy resistance trained
males.
Effects of eight weeks of time-restricted feeding (16/8)
on basal metabolism, maximal strength, body composition,
inflammation and cardiovascular risk factors in trained
males
Moro et al., 2016
J. Trans. Med., Italy
34 trained males
ND
Between 8 AM to 8 PM
3 hr/day training
Anthropometric measurements
Hormonal level
TC, HDL, LDL & TG
Divided into 1, 4 & 8 pm
100% in 16:8 window
TRF
Energy:
2828 ± 412.3 kcal/day
CHO- 53.20 ± 1.40%
Fat- 24.70 ± 3.10%
Protein 22.10 ± 2.60%
Energy:
3007 ± 444.70 kcal/day
CHO- 54.70 ± 2.20%
Fat- 23.90 ± 3.50%
Protein 21.40 ± 1.80%
Table. 1. Major results of experiments
IF pre IF post ND pre ND post
FFM (kg) 73.0 73.72 73.93 74.41
FM (kg) 10.90 9.28 11.36 11.05
Adiponectin (µg/mL) 11.8 13.9 10.8 10.90
Leptin (ng/mL) 0.21 0.2 0 0.24 0.24
TNF- α(ng/L) 5.58 5.13 5.69 5.68
Testosterone (nmol/L) 21.26 21.23 18.60 18.85
IGF -1 (ng/mL) 216.94 216.12 215.59 215.51
IF pre IF post ND pre ND post
Insulin (mU/L) 2.78 1.77 2.56 2.82
TSH (mU/L) 1.28 1.27 1.30 1.31
T3 (ng/dL) 83.21 74.32 81.12 82.35
Glucose (mg/dL) 96.64 85.92 95.21 96.02
Total cholesterol
(mg/dL)
193.45 191.37 196.33 197.12
Cortisol (ng/mL) 174.25 186.05 191.24 185.78
HDL (mg/dL) 54.11 58.06 53.33 54.12
LDL (mg/dL) 114.58 110.26 115.58 116.08
TG (mg/dL) 123.78 115.23 137.10 134.58
REE (kcal/day) 1880 1991 1901 1895
RR 0.83 0.81 0.83 0.83
Conclusion
• TRF could be beneficial in resistance trained
individuals to improve health related biomarkers,
also deceases FM & maintain muscle mass.
• Regimen- adopt by athletes.
Objective:
To compare the feasibility & effectiveness of IER /
CER for weight loss, insulin sensitivity & other
metabolic disease risk markers.
The effect of Intermittent fasting or continuous energy
restriction on weight loss and metabolic disease risk markers:
a randomized trail in young overweight women
Harvie et al., 2011
Int. J. Obes., London
Changes in dietary intake, weight and also physical activity levels
At 1, 3 and 6 months
6 Months experiment
Analyzed for metabolic disease risk markers
107 Randomized samples
53 assigned to IER 54 assigned to CER
Fig .1. Study design
Parameters Base line 1
month
3
month
6 month
Energy (kcal/d)
IER 1908.4 1348.6 1341.0 1340.9
CER 1894.3 1425.5 1484.3 1506.8
Protein (g/d)
IER 80.3 73.2 72.1 70.7
CER 77.3 75.9 74.6 73.4
Fat (g/d)
IER 73.0 43.3 43.7 43.7
CER 73.2 48.1 52.6 56.4
Saturated fat (g/d)
IER 27.1 14.3 15.5 15.1
CER 26.4 16.3 16.5 16.8
Carbohydrates (g/d)
IER 220.9 164.7 163.8 161.0
CER 227.5 180.0 184.2 189.8
Fibre (g/d)
IER 13.6 13.2 12.8 11.90
CER 13.9 14.9 14.9 15.9
MET (mins/d)
IER 178.1 245.3 236.7 232.1
CER 218.0 300.0 326.2 373.9
Table. 1. Changes in dietary intake and physical activity
Parameters Base line 1 month 3 month 6 month
Insulin (µU/ml) IER 7.3 6.4 5.6 5.2
CER 7.4 6.5 6.3 6.3
Glucose (mmol/L) IER 4.8 4.8 4.7 4.7
CER 4.8 4.7 4.7 4.7
Adiponectine (µg/ml) IER 10.6 9.9 10.5 11.7
CER 10.8 9.4 10.4 10.9
Ghrelin (pg/ml) IER 136.0 136.0 134.2 134.0
CER 132.5 130.3 130.0 129.1
BDNF (pg/ml) IER 9539 9538 9621 9630
CER 9898 9896 9910 9982
Ketones (µM) IER 40.8 77.1 73.0 67.6
CER 48.0 71.1 63.3 49.6
Table. 2 . Changes in Insulin related parameters over 6 months
Parameters Base line 1 month 3 month 6 month
Cholesterol (mmol/L)
IER 5.1 4.6 4.8 4.8
CER 5.2 4.8 4.8 4.7
Triglycerides (mmol/L)
IER 1.2 1.0 1.0 1.0
CER 1.3 1.1 1.0 1.0
LDL(mmol/L)
IER 3.1 2.8 2.9 2.8
CER 3.1 2.8 2.8 2.8
BP systolic
IER 115.2 111.6 111.5 110.2
CER 116.8 110.0 110 109.3
BP Diastolic IER 76.7 72.6 72.4 72.4
CER 75.4 71.1 70.5 69.7
Leptin (ng/ml)
IER 28.5 19.4 18.0 17.0
CER 28.2 19.2 19.2 18.0
Leptin/ Adiponectin ratio
ng/μg
IER 1.5 1.4 1.3 1.2
CER 1.5 1.3 1.2 1.2
DHEAS(μmol/L)
Dehydroepi androsterones
IER 3.2 3.4 3.3 3.3
CER 3.4 3.4 3.2 3.3
Table.3 . Changes in risk markers for breast cancer and cardiovascular
diseases over 6 months
Breast cancer risk markers
CVD risk markers
Conclusion
 IER is as effective as CER in regards to weight loss, insulin sensitivity
and other health biomarkers.
 IER can be offered as an alternative equivalent to CER for reducing
obesity and obesity-related disorders .
 Psycho studies are required to better understand behavioural factors
which can promote or reduce compliance to IER and CER regimens.
Practicality of Intermittent Fasting in Humans
and its effect on Oxidative Stress and Genes
Related to Aging
Objective: Investigate an alternative dietary approach,
i.e. intermittent fasting (IF) and its effect on gene expression
of aging and oxidative stress.
Wegman et al., 2015
Rejuvenation Research, Florida
Cohort of 24 healthy individuals -Randomly
3 week treatment periods—IF and IF with anti-oxidant
Supplemented their
diet with placebo
capsules
Supplemented their diet with
Vit C(1g) and E capsules
(400IU)/ orally
Blood samples - beginning and at the end of trial
Gene expression, RNA/ DNA oxidation were measured
Satisfactory survey
Results were
analyzed
Fig. 1. Trial design
Fig. 2. Gene expression changes
Fig. 3. Nucleotide oxidation changes
Fig. 4. Dietary satisfaction survey results
Conclusion
Detected a marginal increase (2.7%) in SIRT3
expression due to the IF diet, but no change in
expression of other genes or oxidative stress markers.
Additional studies are in need to assess how
oxidative stress and anti-oxidants interplay with
dietary restriction to mediate the potential health
effects.
 Although the study suggests that, the IF dieting
paradigm is acceptable in healthy individuals,
additional research is needed to further assess the
potential benefits and risks.
Objective:
To know whether IF enhance Beta cell survival
through Autophagy – lysosomal pathway
Intermittent fasting preserves beta-cell mass on Obesity –
induced Diabetes via the Autophagy lysosomal pathway
Liu et al., 2017
Autophagy, Germany
• 8 weeks old mice: N= 86 (wild & lab mices )
• Divided into two groups
• Chow diet (lab diet): 12 weeks
• High fat diet
• randomized into 2
• IF group & Ad- lib- fed (control): 6 weeks
• 12.00PM to 12.00PM alternate 24hr fasting &
feeding
• Ad- lib- fed was access to water
• Mices were weighed at weekly intervals
• After 6 weeks the animals were sacrificed for
further analysis
Fig.1 . Study design
Figure . 2. Prevention of beta cell loss in mice with diet-induced obesity
Figure. 3. Accumulation of Autophagosome due to Intermittent fasting
A B
Conclusion
Intermittent fasting/ APD preserves
organelle quality via the autophagy-
lysosome pathway to enhance beta cell
survival and stimulates markers of
regeneration in obesity-induced diabetes.
Differential Roles of Unsaturated and Saturated Fatty
Acids on Autophagy and Apoptosis in Hepatocytes
Determine the effects of saturated and
unsaturated fatty acids on autophagy and
apoptosis in hepatocytes.
.
Objective:
Mei, et al., 2011
The J. Phar. and Exptl. Thera
Hep G2 cells
Control
diet
Western diet
(40 % of calorie from milk)
Then treated with- 6hr
Vehicle control OA OA+CQ CQ
(5%BSA) (500µm) (20µm ) (20µm alone)
Fig.1 . Study design
Cell lysates were subjected to Immunoblot analysis
Induction of AP, No. of autosomes were recorded
For 3 months
Then treated with- 6hr
Vehicle control PA PA+CQ PQ
(5%BSA) (500µm) (20µm ) (20µm alone)
CQ: Chloroquine BAF: Bafilomycin
LC3Punctapercell
LC3Punctapercell
A
C D
B
LC3Punctapercell
LC3Punctapercell
C
A B
D
Fig. 4. OA but not PA increases the number of autophagosomes and
lipid droplets in HepG2 cells.
A
CB
D
• OA treated cells tend to increase the LC3 puncta levels in the
presence of CQ and induce autophagy.
• No. of lipid droplets and level of triglycerides were
significantly higher in OA treated HepG2 cells than in PA
treated cells.
• Impaired autophagy in PA-treated cells may increase
mitochondrial damage and further increase apoptosis.
CONCLUSION
Objective: to know the changes in hormones when body knows that it
will be hungry until sunset during RAMDAN & NON- RAMDAN fasting.
Material and methods
30 participants= 19 males + 11 females
Two phase
Blood samples in the noon
Study protocol repeated.
1st phase- skip- Suhur 2nd phase- after 6 months
Table. 1. Demographic characteristics of the participants
Leptin(ng/mL)
Fig .1. Differences in Hormonal levels
Ghrelin(pg/mL)
GLP-1(pg/mL)
Conclusion
Significant differences in leptin, ghrelin, and GLP-
1 levels between Ramadan fasting and non-
Ramadan fasting.
Nervous and Gastro intestinal system may behave
differently in religious than in non- religious
fasting.
IF is an dietary approach, which Switches between fasting
states and feeding states (Switch on: Switch off) or (fast: feed).
TRF could be beneficial in resistance trained individuals to
improve health related biomarkers, by decreasing FM &
maintain muscle mass.
TRF Regimen-could be adopted by athletes.
Intermittent energy restriction is as effective as Continuous
energy restriction in regards to weight loss, insulin sensitivity
and other health biomarkers.
IER can be offered as an alternative equivalent to CER for
reducing obesity and obesity-related disorders.
Intermittent fasting preserves organelle quality via the
autophagy-lysosome pathway to enhance beta cell survival and
stimulates markers of regeneration in obesity-induced diabetes.
Impaired autophagy in saturated fatty acid (Palmitic acid)-treated
cells may increase mitochondrial damage and further increase
apoptosis.
Unsaturated fatty acid (Oleic acid) treated cells tend to increase
the LC3 puncta levels, which induces autophagy.
No. of lipid droplets and level of triglycerides were significantly
higher in OA treated HepG2 cells than in PA treated cells.
Impaired autophagy in saturated fatty acid (Palmitic acid) treated
cells may increase mitochondrial damage and further increase
apoptosis.
 There was a marginal increase (2.7%) in SIRT3 expression due to the
IF diet, but no change in expression of other genes or oxidative
stress markers analyzed.
 Significant difference's in Leptin, Ghrelin, and GLP-1 levels between
Ramadan fasting and non-Ramadan fasting.
 Nervous and Gastro intestinal system may behave differently in
religious than in non- religious fasting.
 Although IF dieting paradigm is acceptable in healthy individuals,
additional research is needed to further assess the potential
benefits and risks.
References
CAKLILI1, O.G., BANU, I., YAVUZ, G., TULU, S. AND AYTEKIN, O., 2017,
Differences in Leptin, Ghrelin, and Glucagon-like peptide-1 levels between religious
fasting and normal fasting. Turk. J. Med. Sci, 47: 1152-1156.
DERETIC, V., SAITOH, T. AND AKIRA, S., 2013, Autophagy in infection,
inflammation and immunity. Nat. Rev. Immunol. 13(10):722-737.
EEVA, L. E., SKELINEN, L. AND SAFTIG, H., 2012, Autophagy: A lysosomal
degradation pathway with a central role in health and disease. Biochemica et
Biophysica Acta, 12(4):664-673.
HARVIE, M.N., PEGINGTON, M., MATTSON, M.P., FRYSTYK, J., DILLON, F.,
GARETH, E., JACK, C., OLGA, D., JOSEPHINE, M., EGAN, K., ALLAN, F. AND
ANTHONY, H., 2011, The effects of Intermittent or Continuous energy restriction on
weight loss and metabolic disease risk markers: a randomized trial in young
overweight women. Int. J. Obes, 35(5): 714–727.
LIU, H., ALI, J., NIDHI, R., MAHADEVAN, J. AND PAUL, S., 2017, Intermittent
Fasting Preserves Beta-Cell Mass in Obesity-induced Diabetes via the Autophagy-
Lysosome Pathway. Autophagy, 26: 1-14.
MORO, T., TINSLEY, G., BIANCO, A. AND PAOLI, A.L, 2016, Effects of eight
weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength,
body composition, inflammation and cardiovascular risk factors in trained males. J.
Transl. Med, 14: 290.
MEI, S., NI, H.M., MANLEY, S., BRYAN, L., COPPLE, Z. AND DING, W.N., 2011,
Differential Roles of Unsaturated and Saturated fatty Acids on Autophagy and
Apoptosis in Hepatocytes, The J. of Phar. and Expe. Thera, 11(3):487–498,
RIZZA AND WANNA, 2017, The fast mimicking diet- recent advances in clinical
experimental research on dementia and neurodegenerative disorders. The Ita.. Neu.
Ass. 13(2): 173-194.
WEGMAN, M. P., MICHAEL, H. G., DOUGLAS, M. B., MEENA, N. S., STEPHEN,
M. AND CHRZANOWSKI, 2015, Practicality of Intermittent Fasting in Humans
and its effect on oxidative stress and genes related to aging and metabolism.
Rejuvenation Research, 18 (2): 162-182.
YANG, Z.J., CHEE, C.E, HUANG, S. AND SINICROPE, F.A., 2012, The role of
Autophagy in Cancer: Therapeutic Implications. Mol Cancer Ther. 10(9): 1533-
1541.
XIE , X., WEIJIE , Y., PIWEI, Z ., HUI , Y., 2017, Green Tea Polyphenols, Mimicking
the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury
via Regulating Autophagy Flux, Nutrients. 2017, 31(9), 497-512.
Intermittent fasting and Autophagy

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Intermittent fasting and Autophagy

  • 1. Dr. Sudharani, N. Assistant Professor (Food Science and Nutrition) College of Horticulture Mudigere, Karnataka-577132
  • 2. One time eater – YoGi Two time eater – Bhogi Three time eater – Hothkondogi
  • 5. Types of fasting(Dietary restriction) • Calorie Restriction - CR: Chronic reduction of 20-40% of the caloric intake. • Prolonged Fasting - PF: which lasts more than 72 hr (4-7 days). • Fast Mimicking Diet - FMD: Prolonged and periodic fasting protocol which does not consider the whole abstinence from food. • Intermittent Fasting - IF: Rizza and Wanna, 2017
  • 6. Intermittent fasting • Switching between fasting states and feeding states (Switch on: Switch off) or (fast: feed). • This fasting state can last 16 to 48 hrs and IF can be combined with any dietary protocol.
  • 7. 3 Meals a day with regular snacking
  • 8. Example of following an IF (TRF) protocol
  • 9. Fat burning during fastingFatStorageFatburning Hours since last meal
  • 10. Insulin Response to Macronutrients FatStorageFatburning Hours since last meal Fat Protein Fasting Carbohy drates Insulin
  • 11. Ways to undertake Intermittent fasting Time restricted eating Alternative day fasting Weekly IF Rizza and Wanna, 2017
  • 12. How to get started How to do IF “One size doesn’t fit all”
  • 13. Lean gains Daily Intermittent Fasting (TRF) 16–hour fast : 8–hour eating period
  • 14.
  • 15. Weekly Intermittent Fasting One 24-hour fast each week In this example, lunch on Monday is your last meal of the day. You then fast until lunch on Tuesday.
  • 16.
  • 17. Alternate Day Intermittent Fasting (Warrior diet) Fast for alternating 24-hour periods (20:4)  Ori Hofmekler This style of intermittent fasting is often used in research studies. But it is not very popular in the real world.
  • 18.
  • 19.
  • 20.
  • 21. Benefits of IF  Loose weight  Reduces  CVD  Diabetes  Aging process  Cleans cells & Rejuvenate  Induce Autophagy Eating Disorder Body Dysmorphia Type 1 Diabetes Pregnant or Breastfeeding Medication
  • 22. Derived from Greek words “auto” meaning self and “phagy” means eating. Autophagy is a normal physiological process of catabolic degradation where protein and organelles are engulfed into autophagosomes, digested in lysosomes and recycled to sustain cellular metabolism during stress. Survival, Development and Homeostasis
  • 23. Dr. , Nobel Laureate, 2016
  • 24. Schematic presentation of Autophagosome formation
  • 25. Types of AP • Macro AP • Micro AP • Chaperone AP
  • 26.
  • 27. Growth/ proliferation Recycle nutrients Autopahgic cell death Cellular stress Starvation mTOR Energy Infection controlProteostasis Organelle Homeostasis HEALTH & DISEASE
  • 28. • mTOR- protein kinase. • Links and acts as core component. • Central regulator of metabolism and physiology • Regulates cell growth, proliferation, motility, survival, protein synthesis, transcription and autophagy. • mTOR inhibition autophagy. • AMP-activated protein kinase • master regulator of cellular energy homeostasis. • activated in stresses • During glucose starvation, the ratio of AMP :ATP increases, leading to the activation of AMPK. • AMPK stimulates the autophagy Regulation of AP
  • 29. Zhineng et al., 2011 & Eeva et al., 2009 Atg 5- cardiomyopathy
  • 30. Xie et al., 2017 Calorie restriction mimetics (CRM)
  • 31. • Aging • High carbohydrates • Frequent meal consumption • High Insulin
  • 32.
  • 33. Objective: Investigate the effect of a modified Intermittent Fasting protocol (TRF) in healthy resistance trained males. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation and cardiovascular risk factors in trained males Moro et al., 2016 J. Trans. Med., Italy
  • 34. 34 trained males ND Between 8 AM to 8 PM 3 hr/day training Anthropometric measurements Hormonal level TC, HDL, LDL & TG Divided into 1, 4 & 8 pm 100% in 16:8 window TRF Energy: 2828 ± 412.3 kcal/day CHO- 53.20 ± 1.40% Fat- 24.70 ± 3.10% Protein 22.10 ± 2.60% Energy: 3007 ± 444.70 kcal/day CHO- 54.70 ± 2.20% Fat- 23.90 ± 3.50% Protein 21.40 ± 1.80%
  • 35. Table. 1. Major results of experiments IF pre IF post ND pre ND post FFM (kg) 73.0 73.72 73.93 74.41 FM (kg) 10.90 9.28 11.36 11.05 Adiponectin (µg/mL) 11.8 13.9 10.8 10.90 Leptin (ng/mL) 0.21 0.2 0 0.24 0.24 TNF- α(ng/L) 5.58 5.13 5.69 5.68 Testosterone (nmol/L) 21.26 21.23 18.60 18.85 IGF -1 (ng/mL) 216.94 216.12 215.59 215.51
  • 36. IF pre IF post ND pre ND post Insulin (mU/L) 2.78 1.77 2.56 2.82 TSH (mU/L) 1.28 1.27 1.30 1.31 T3 (ng/dL) 83.21 74.32 81.12 82.35 Glucose (mg/dL) 96.64 85.92 95.21 96.02 Total cholesterol (mg/dL) 193.45 191.37 196.33 197.12 Cortisol (ng/mL) 174.25 186.05 191.24 185.78 HDL (mg/dL) 54.11 58.06 53.33 54.12 LDL (mg/dL) 114.58 110.26 115.58 116.08 TG (mg/dL) 123.78 115.23 137.10 134.58 REE (kcal/day) 1880 1991 1901 1895 RR 0.83 0.81 0.83 0.83
  • 37. Conclusion • TRF could be beneficial in resistance trained individuals to improve health related biomarkers, also deceases FM & maintain muscle mass. • Regimen- adopt by athletes.
  • 38. Objective: To compare the feasibility & effectiveness of IER / CER for weight loss, insulin sensitivity & other metabolic disease risk markers. The effect of Intermittent fasting or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trail in young overweight women Harvie et al., 2011 Int. J. Obes., London
  • 39. Changes in dietary intake, weight and also physical activity levels At 1, 3 and 6 months 6 Months experiment Analyzed for metabolic disease risk markers 107 Randomized samples 53 assigned to IER 54 assigned to CER Fig .1. Study design
  • 40. Parameters Base line 1 month 3 month 6 month Energy (kcal/d) IER 1908.4 1348.6 1341.0 1340.9 CER 1894.3 1425.5 1484.3 1506.8 Protein (g/d) IER 80.3 73.2 72.1 70.7 CER 77.3 75.9 74.6 73.4 Fat (g/d) IER 73.0 43.3 43.7 43.7 CER 73.2 48.1 52.6 56.4 Saturated fat (g/d) IER 27.1 14.3 15.5 15.1 CER 26.4 16.3 16.5 16.8 Carbohydrates (g/d) IER 220.9 164.7 163.8 161.0 CER 227.5 180.0 184.2 189.8 Fibre (g/d) IER 13.6 13.2 12.8 11.90 CER 13.9 14.9 14.9 15.9 MET (mins/d) IER 178.1 245.3 236.7 232.1 CER 218.0 300.0 326.2 373.9 Table. 1. Changes in dietary intake and physical activity
  • 41. Parameters Base line 1 month 3 month 6 month Insulin (µU/ml) IER 7.3 6.4 5.6 5.2 CER 7.4 6.5 6.3 6.3 Glucose (mmol/L) IER 4.8 4.8 4.7 4.7 CER 4.8 4.7 4.7 4.7 Adiponectine (µg/ml) IER 10.6 9.9 10.5 11.7 CER 10.8 9.4 10.4 10.9 Ghrelin (pg/ml) IER 136.0 136.0 134.2 134.0 CER 132.5 130.3 130.0 129.1 BDNF (pg/ml) IER 9539 9538 9621 9630 CER 9898 9896 9910 9982 Ketones (µM) IER 40.8 77.1 73.0 67.6 CER 48.0 71.1 63.3 49.6 Table. 2 . Changes in Insulin related parameters over 6 months
  • 42. Parameters Base line 1 month 3 month 6 month Cholesterol (mmol/L) IER 5.1 4.6 4.8 4.8 CER 5.2 4.8 4.8 4.7 Triglycerides (mmol/L) IER 1.2 1.0 1.0 1.0 CER 1.3 1.1 1.0 1.0 LDL(mmol/L) IER 3.1 2.8 2.9 2.8 CER 3.1 2.8 2.8 2.8 BP systolic IER 115.2 111.6 111.5 110.2 CER 116.8 110.0 110 109.3 BP Diastolic IER 76.7 72.6 72.4 72.4 CER 75.4 71.1 70.5 69.7 Leptin (ng/ml) IER 28.5 19.4 18.0 17.0 CER 28.2 19.2 19.2 18.0 Leptin/ Adiponectin ratio ng/μg IER 1.5 1.4 1.3 1.2 CER 1.5 1.3 1.2 1.2 DHEAS(μmol/L) Dehydroepi androsterones IER 3.2 3.4 3.3 3.3 CER 3.4 3.4 3.2 3.3 Table.3 . Changes in risk markers for breast cancer and cardiovascular diseases over 6 months Breast cancer risk markers CVD risk markers
  • 43. Conclusion  IER is as effective as CER in regards to weight loss, insulin sensitivity and other health biomarkers.  IER can be offered as an alternative equivalent to CER for reducing obesity and obesity-related disorders .  Psycho studies are required to better understand behavioural factors which can promote or reduce compliance to IER and CER regimens.
  • 44. Practicality of Intermittent Fasting in Humans and its effect on Oxidative Stress and Genes Related to Aging Objective: Investigate an alternative dietary approach, i.e. intermittent fasting (IF) and its effect on gene expression of aging and oxidative stress. Wegman et al., 2015 Rejuvenation Research, Florida
  • 45. Cohort of 24 healthy individuals -Randomly 3 week treatment periods—IF and IF with anti-oxidant Supplemented their diet with placebo capsules Supplemented their diet with Vit C(1g) and E capsules (400IU)/ orally Blood samples - beginning and at the end of trial Gene expression, RNA/ DNA oxidation were measured Satisfactory survey Results were analyzed Fig. 1. Trial design
  • 46. Fig. 2. Gene expression changes
  • 47. Fig. 3. Nucleotide oxidation changes
  • 48. Fig. 4. Dietary satisfaction survey results
  • 49. Conclusion Detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers. Additional studies are in need to assess how oxidative stress and anti-oxidants interplay with dietary restriction to mediate the potential health effects.  Although the study suggests that, the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.
  • 50. Objective: To know whether IF enhance Beta cell survival through Autophagy – lysosomal pathway Intermittent fasting preserves beta-cell mass on Obesity – induced Diabetes via the Autophagy lysosomal pathway Liu et al., 2017 Autophagy, Germany
  • 51. • 8 weeks old mice: N= 86 (wild & lab mices ) • Divided into two groups • Chow diet (lab diet): 12 weeks • High fat diet • randomized into 2 • IF group & Ad- lib- fed (control): 6 weeks • 12.00PM to 12.00PM alternate 24hr fasting & feeding • Ad- lib- fed was access to water • Mices were weighed at weekly intervals • After 6 weeks the animals were sacrificed for further analysis Fig.1 . Study design
  • 52. Figure . 2. Prevention of beta cell loss in mice with diet-induced obesity
  • 53. Figure. 3. Accumulation of Autophagosome due to Intermittent fasting A B
  • 54. Conclusion Intermittent fasting/ APD preserves organelle quality via the autophagy- lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes.
  • 55. Differential Roles of Unsaturated and Saturated Fatty Acids on Autophagy and Apoptosis in Hepatocytes Determine the effects of saturated and unsaturated fatty acids on autophagy and apoptosis in hepatocytes. . Objective: Mei, et al., 2011 The J. Phar. and Exptl. Thera
  • 56. Hep G2 cells Control diet Western diet (40 % of calorie from milk) Then treated with- 6hr Vehicle control OA OA+CQ CQ (5%BSA) (500µm) (20µm ) (20µm alone) Fig.1 . Study design Cell lysates were subjected to Immunoblot analysis Induction of AP, No. of autosomes were recorded For 3 months Then treated with- 6hr Vehicle control PA PA+CQ PQ (5%BSA) (500µm) (20µm ) (20µm alone)
  • 57. CQ: Chloroquine BAF: Bafilomycin LC3Punctapercell LC3Punctapercell A C D B
  • 59. Fig. 4. OA but not PA increases the number of autophagosomes and lipid droplets in HepG2 cells. A CB D
  • 60. • OA treated cells tend to increase the LC3 puncta levels in the presence of CQ and induce autophagy. • No. of lipid droplets and level of triglycerides were significantly higher in OA treated HepG2 cells than in PA treated cells. • Impaired autophagy in PA-treated cells may increase mitochondrial damage and further increase apoptosis. CONCLUSION
  • 61. Objective: to know the changes in hormones when body knows that it will be hungry until sunset during RAMDAN & NON- RAMDAN fasting.
  • 62. Material and methods 30 participants= 19 males + 11 females Two phase Blood samples in the noon Study protocol repeated. 1st phase- skip- Suhur 2nd phase- after 6 months
  • 63. Table. 1. Demographic characteristics of the participants
  • 64. Leptin(ng/mL) Fig .1. Differences in Hormonal levels Ghrelin(pg/mL) GLP-1(pg/mL)
  • 65. Conclusion Significant differences in leptin, ghrelin, and GLP- 1 levels between Ramadan fasting and non- Ramadan fasting. Nervous and Gastro intestinal system may behave differently in religious than in non- religious fasting.
  • 66. IF is an dietary approach, which Switches between fasting states and feeding states (Switch on: Switch off) or (fast: feed). TRF could be beneficial in resistance trained individuals to improve health related biomarkers, by decreasing FM & maintain muscle mass. TRF Regimen-could be adopted by athletes. Intermittent energy restriction is as effective as Continuous energy restriction in regards to weight loss, insulin sensitivity and other health biomarkers. IER can be offered as an alternative equivalent to CER for reducing obesity and obesity-related disorders.
  • 67. Intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes. Impaired autophagy in saturated fatty acid (Palmitic acid)-treated cells may increase mitochondrial damage and further increase apoptosis. Unsaturated fatty acid (Oleic acid) treated cells tend to increase the LC3 puncta levels, which induces autophagy. No. of lipid droplets and level of triglycerides were significantly higher in OA treated HepG2 cells than in PA treated cells. Impaired autophagy in saturated fatty acid (Palmitic acid) treated cells may increase mitochondrial damage and further increase apoptosis.
  • 68.  There was a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed.  Significant difference's in Leptin, Ghrelin, and GLP-1 levels between Ramadan fasting and non-Ramadan fasting.  Nervous and Gastro intestinal system may behave differently in religious than in non- religious fasting.  Although IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.
  • 69.
  • 70. References CAKLILI1, O.G., BANU, I., YAVUZ, G., TULU, S. AND AYTEKIN, O., 2017, Differences in Leptin, Ghrelin, and Glucagon-like peptide-1 levels between religious fasting and normal fasting. Turk. J. Med. Sci, 47: 1152-1156. DERETIC, V., SAITOH, T. AND AKIRA, S., 2013, Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 13(10):722-737. EEVA, L. E., SKELINEN, L. AND SAFTIG, H., 2012, Autophagy: A lysosomal degradation pathway with a central role in health and disease. Biochemica et Biophysica Acta, 12(4):664-673. HARVIE, M.N., PEGINGTON, M., MATTSON, M.P., FRYSTYK, J., DILLON, F., GARETH, E., JACK, C., OLGA, D., JOSEPHINE, M., EGAN, K., ALLAN, F. AND ANTHONY, H., 2011, The effects of Intermittent or Continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int. J. Obes, 35(5): 714–727.
  • 71. LIU, H., ALI, J., NIDHI, R., MAHADEVAN, J. AND PAUL, S., 2017, Intermittent Fasting Preserves Beta-Cell Mass in Obesity-induced Diabetes via the Autophagy- Lysosome Pathway. Autophagy, 26: 1-14. MORO, T., TINSLEY, G., BIANCO, A. AND PAOLI, A.L, 2016, Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation and cardiovascular risk factors in trained males. J. Transl. Med, 14: 290. MEI, S., NI, H.M., MANLEY, S., BRYAN, L., COPPLE, Z. AND DING, W.N., 2011, Differential Roles of Unsaturated and Saturated fatty Acids on Autophagy and Apoptosis in Hepatocytes, The J. of Phar. and Expe. Thera, 11(3):487–498, RIZZA AND WANNA, 2017, The fast mimicking diet- recent advances in clinical experimental research on dementia and neurodegenerative disorders. The Ita.. Neu. Ass. 13(2): 173-194.
  • 72. WEGMAN, M. P., MICHAEL, H. G., DOUGLAS, M. B., MEENA, N. S., STEPHEN, M. AND CHRZANOWSKI, 2015, Practicality of Intermittent Fasting in Humans and its effect on oxidative stress and genes related to aging and metabolism. Rejuvenation Research, 18 (2): 162-182. YANG, Z.J., CHEE, C.E, HUANG, S. AND SINICROPE, F.A., 2012, The role of Autophagy in Cancer: Therapeutic Implications. Mol Cancer Ther. 10(9): 1533- 1541. XIE , X., WEIJIE , Y., PIWEI, Z ., HUI , Y., 2017, Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux, Nutrients. 2017, 31(9), 497-512.