Effects of Intermittent Fasting on Metabolism and Athletic Performance

RAFAEL

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What is Fasting?

• Fasting in general: Restricting all food or specific food for a period of time.
• Caloric restriction: Reduction of a certain amount of kilocalories well below the number of kilocalories consumed ad libitum
• Dietary restriction: Reduction of a particular or total amount of nutrient intake (protein, lipids, carbohydrates) with nominal or no decrease in total caloric intake

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Colman et al., 2014; Bales & Kraus, 2013; Katewa & Kapahi, 2010 & Ahmed et al., 2018

Types of Intermittent Fasting

• Intermittent fasting (IF) is essentially fasting alone or with a restriction of calories during specific and scheduled periods of time.
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• 16/8 fasting
• 5:2 fasting: Restricting calorie intake 25% 2 days/wk and eating normally the rest of the days
• Full day fasting: 1 to 2 days/wk and eating normally the other 5 or 6 days/wk
• “The warrior diet”: fasting for 20 hours during the day and eating 1 large meal at night
• Ramadan Fasting: no fluid/food (sunrise to sunset)

Why do people fast intermittently?

• Religious/Spiritual Practice (i.e. Ramadan)
• Spiritual reflection, self-improvement, a heightened devotion and worship, and inspiration to feel compassionate to those in need.

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• Health benefits: Weight control, increased energy, cognitive performance, cancer, coronary heart diseases, biomarkers for oxidative stress, type 2 diabetes, insulin sensitivity etc.

Ahmed et al., 2018

Common Claimed Benefits of IF

• Promotion of cellular repair and autophagy
• Reduction of insulin resistance
• Decreased LDL cholesterol or “bad” cholesterol
• Longevity promotion
• Prevention of an array of conditions: CVDs, renal diseases, different forms of cancers, and diabetes (type 2 diabetes)
• Protects against neurodegenerative diseases such as Alzheimer’s and Parkinson’s
• Improves memory and boosts brain function

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Ahmed et al., 2018

Discussion Question

It is said that IF is an emerging avenue and has superior outcomes than other fasting strategies.

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What adaptations do you think would occur during IF?

Intermittent Fasting Impact on Metabolism

IF Effect on BMI

• Reduction in total body weight/body fat
• High degree of CR among IF strategies (ADMF or ADF) showed significant body weight reductions
• Whereas, low degree of CR using TRF IF diet showed small body weight reductions
• Compared to continuous CR diet: IF = higher retention of lean body mass (bones, muscle, skin, blood vessels)
• There are many contradictions about whether IF decreases, sustains, or improves lean mass

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Anton et al., 2019; Cho, Y., et al. 2019; Schübel et al., 2018

Discussion Question

Why IF could potentially retain more lean tissue mass preservation vs. continuous calorie restriction?

IF Effect on Lipolysis/Lipid Metabolism

• Increase in lipolysis
• Increase lipid metabolism
• Due to decreased plasma glucose and glycogen stores
• Increased ketone bodies in blood
• Brain, RBC, renal medulla, & rest of body

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Cho, Y., et al. 2019

Anton et al., 2019

IF Effects on Hormones/Clinical Markers

• Decreased leptin
• Ghrelin levels did not change very much throughout interventions
• Little research on chronic leptin and ghrelin hormone levels and IF
• Increased adiponectin levels
• Decreased C-reactive protein (Marker of inflammation)
• Increased norepinephrine
• Decreased insulin levels

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Alzoghaibi et al., 2014; Anton et al., 2019; Cho, Y., et al. 2019

Elderly/Obese/Diabetes

• Improved insulin resistance (HOMA-IR)
• Decreased body fat- (reduced triglyceride levels due to stressing lipolysis & fat metabolism)
• Decreased LDL and increased HDL (recent human trials)
• Decreased insulin levels
• Improved insulin sensitivity (reverse insulin resistance)
• Decreased plasma glucose
• Improved fasting blood glucose
• Overall, improved glucose metabolism

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Ahmed et al., 2018; Cho, Y., et al. 2019; Wei, S. et al. 2018

Elderly/Obese/Diabetes cont.

• Reduced blood pressure (hypertension)
• Reduced RHR
• Improved cardiovascular health

Anton et al., 2019

Anton et al., 2019

IF Effect on Glucose Metabolism

• Major claim of IF is the effect on blood glucose levels
• Decreased blood glucose and increased blood ketone concentration after IF

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Toija, B., et al. 2019

Wei, S. et al. 2018, Cho, Y., et al. 2019

One study showed reduced level of fasting glucose, improved glucose tolerance and insulin sensitivity in type 2 diabetic subjects.

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• Other studies suggest no real difference in fasting glucose levels due to IF
• One meta analysis showed a 3% to 6% decrease in fasting glucose in patients with prediabetes, whereas no significant effect on fasting glucose concentration was observed in healthy individuals.

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Diabetes and insulin resistance cause malfunction in the activation step in the Phosphoinositide 3-kinase/Protein Kinase B, P13K/AKT cascade/pathway.

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IF allows for lower blood glucose levels to combat hyperglycemia

Why recommend IF to diabetics?

Mougios, V. 2016

IF and Diabetes

• Insulin resistance shown to improve with caloric restriction.
• Improved fasting and postprandial glucose levels.
• May improve various metabolic and inflammatory pathways.
• Increased heat shock protein, promoting cellular autophagy, reducing advanced glycation end products, increased adiponectin, and decreased inflammation cytokines
• Improved function of Beta cells in pancreatic islets

Grajower, M., Horne, B. 2019

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Wei, S. et al. 2018

Is IF appropriate for type 2 diabetics?

• Many would recommend that type 2 diabetics eat every 2-3 hours to maintain appropriate blood glucose levels
• The highest risk for hypoglycemia is found in those who take common forms of diabetes medication (insulin)
• Some studies suggest that IF can even increase blood glucose levels due to increased amounts of cortisol.
• Other risks

Qasrawi, S. O., Pandi-Perumal, S. R., & BaHammam, A. S. 2017

IF Effect on Cancer Metabolism

• Cancer cells have more insulin trans-membrane receptor sites to increase the uptake of glucose
• Cancer cells have reduced activity of succinyl-CoA: 3-ketoacid CoA transferase, the rate-controlling step for utilizing β-hydroxybutyrate as a respiratory fuel.
• Normal body cells are more flexible

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• Is is then possible to starve cancer cells while protecting normal cells?

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Ahmed, A. et al. 2018

1. Can promote autophagy induction in tumor cells.
2. May oppose the Warburg effect
3. ROS production from oxidative stress
4. The increase in the ADP/ATP ratio can activate the AMPK pathway

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• Limitations of IF Cancer research

Atunes, F., et al. 2018, Lv, M., Zhu, X., Wang, H., Wang, F., Guan, W., 2014

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Intermittent Fasting Impact on Performance

Anaerobic performance, aerobic performance, and force production

Discussion Question

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Given the metabolic adaptations occurring during IF, how would you expect performance to be affected?

IF effects on force production

• Decrease in neural drive
• Psychological factors
• Sleep disruption affect cognitive centers of CNS and motivation
• Increased levels of plasma sodium and potassium concentrations

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(Gueldich et al., 2019)

IF effects on aerobic and anaerobic performance

• May be time-of-day dependent
• Dehydration
• Metabolic changes
• Decrease in glycogen reserves
• Disrupted sleep patterns

(Naharudin & Yusof, 2018)

Alleviating Negative Effects on Performance

• Maintain hydration levels and caloric intake
• Modify training variables (i.e., intensity, volume, and frequency)
• Incorporate protocols for psychological variables

Intermittent Fasting Impact on Cognition

Memory, anxiety, and stress.

IF and Exercise

• Lack of exercise can lead to an increased risk in various diseases.
• Regular exercise can elicit positive changes in energy expenditure, oxidative damage, insulin sensitivity, as well as synaptic transmission and overall cognitive function.
• Many of the significant effects seen with exercise are achievable through diet as well.
• Greater effects seen when used together.

Liu et al., 2019

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IF and Cognition

• IF has been shown to improve cognitive function
• hippocampus (cognitive processing), striatum (control of body movements), hypothalamus (control of food intake and body temperature), and brainstem (control of cardiovascular and digestive systems)
• Protects and enhances neurons by increased expression of BDNF
• Reduces cognitive deficiencies by downregulating pro-inflammatory cytokines 1L-10 & 1L-1B

Cherif et al., 2016

IF and BDNF

• Brain Derived Neurotrophic Factor is a protein that helps grow and maintain never cells.
• BDNF regulates synaptic plasticity, neurogenesis, and longevity of neurons in adults.
• BDNF functionality is essential to learning and to maintaining memory capacity in humans.

Cherif et al., 2016

IF and Cognition

• IF promotes BDNF production.
• When IL-1B is upregulated, BDNF is expressed less.
• Promotes neuron/synaptic integrity and improved cognitive function
• IF has been shown to be a preventative or an effective post-ischemia treatment

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Cherif et al., 2016; Hu, et al., 2019

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IF and Ischemia

• IF as a treatment for ischemia after acute event.
• sham operation and ad libitum feeding (Sham-AL); (2) 2VO operation and ad libitum feeding (2VO-AL); or (3) 2VO operation and IF (2VO-IF)
• Novel Object Recognition Test and Morris Water Maze Test
• IF prevented BDNF decrease and inflammatory cytokine increase

Hu, et al., 2019

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Hu, et al., 2019

IF and Cognition

• IF has been shown to improve mood, memory, and spatial learning
• GABA is an inhibitory neurotransmitter that reduces excitability throughout the nervous system
• GABAergic tone is enhanced, reducing anxiety

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Liu et al., 2019

Cherif et al., 2016

Cherif et al., 2016

Discussion Question

What part(s) of the brain are most affected by an intermittent fasting treatment?

Recap

• Metabolic adaptations:
• BMI/fat mass
• Insulin resistance
• Chronic diseases
• IF improved cellular metabolism by utilizing lipolysis
• Performance Adaptation:
• Blunt muscle force abilities
• Decrease anaerobic power output
• Improved mental function
• Effective post-treatment for ischemia

Issues with Intermittent Fasting

• High drop-out rate
• Increased chance of over indulging after fasting
• Risk of dangerous levels of calorie deprivation
• Not safe for special populations:
• Children, Underweight, Pregnant, Eating disorders
• Influences sleep patterns and duration
• Cortisol has a circadian rhythm

Schübel et al., 2018

Overall Limitations

• Non-standardized dietary control of the patient
• Low compliance
• Sample size
• Difficulty conducting a study covering long periods of time
• Difficulty setting the control group (making it difficult to identify the beneficial effects of an IFD)
• Most studies are animal trials
• Lack of nutrient quality and quantity intake assessment

Future Studies

• Future Research
• Effects of IF during various seasons
• Investigate performance levels during endurance and ultra-endurance events
• Chronic effects of IF
• Assess nutrient quality and quantity before and after IF
• Measure sleep quality
• More human trials

References

• Anton, S. D., Moehl, K., Donahoo, W. T., Marosi, K., Lee, S. A., Mainous, A. G., III, Mattson, M. P. (2019). flipping the metabolic switch: understanding and applying the health benefits of fasting. OBESITY, 26(2), 254–268.
• Ahmed, A., Saeed, F., Arshad, M. U., Afzaal, M., Imran, A., Ali, S. W., Imran, M. (2018). Impact of intermittent fasting on human health: an extended review of metabolic cascades. International Journal of Food Properties, 21(1), 2700–2713.
• Alzoghaibi, M. A., Pandi-Perumal, S. R., Sharif, M. M., & BaHammam, A. S. (2014). Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels. Plos One, 9(3),
• Bales, C. W., & Kraus, W. E. (2013). Caloric restriction: implications for human cardiometabolic health. Journal of cardiopulmonary rehabilitation and prevention, 33(4), 201–208. doi:10.1097/HCR.0b013e318295019e
• Katewa, S. D., & Kapahi, P. (2010). Dietary restriction and aging. Aging cell, 9(2), 105–112. doi:10.1111/j.1474-9726.2010.00552.x
• Gueldich, H., Zghal, F., Borji, R., Chtourou, H., Sahli, S., & Rebai, H. (2019). The effects of ramadan intermittent fasting on the underlying mechanisms of force production capacity during maximal isometric voluntary contraction. Chronobiology International: The Journal of Biological & Medical Rhythm Research, 36(5), 698–708.
• Chtourou, H., Hammouda, O., Chaouachi, A., Chamari, K., & Souissi, N. (2012). The effect of time-of-day and ramadan fasting on anaerobic performances. International Journal of Sports Medicine, 33(2), 142–147
• Shephard R. J. (2012). The impact of ramadan observance upon athletic performance. Nutrients, 4(6), 491–505. doi:10.3390/nu4060491

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References Cont.

• Cherif, A., Roelands, B., Meeusen, R., & Chamari, K. (2016). Effects of intermittent fasting, caloric restriction, and ramadan intermittent fasting on cognitive performance at rest and during exercise in adults. Sports Medicine, 46(1), 35.
• Liu, Y., Cheng, A., Li, Y.-J., Yang, Y., Kishimoto, Y., Zhang, S., Mattson, M. P. (2019). SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice. Nature communications, 10.
• Hu, Y., Zhang, M., Chen, Y., Yang, Y., & Zhang, J. (2019). Postoperative intermittent fasting prevents hippocampal oxidative stress and memory deficits in a rat model of chronic cerebral hypoperfusion. European Journal of Nutrition, 58(1), 423-432. doi:10.1007/s00394-018-1606-4
• Wilson, R. A., Deasy, W., Stathis, C. G., Hayes, A., & Cooke, M. B. (2018). Intermittent fasting with or without exercise prevents weight gain and improves lipids in diet-induced obese mice. Nutrients, 10(3), 346.
• Toija, B., et al. 2019 Mimicking the Fasting Mimicking Diet Retrieved from https://www.quantifiedbob.com/fasting-mimicking-diet/
• Wei, S. et al. 2018 Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores β cells and reconstructs gut microbiota in mice. Nutr Metab (Lond) 15, 80 (2018) doi:10.1186/s12986-018-0318-3
• Grajower, M. M., & Horne, B. D. (2019). Clinical Management of Intermittent Fasting in Patients with Diabetes Mellitus. Bariatric Times, 16(6), 18–22.

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References Cont.

• Moraes, R. C. M. de, Portari, G. V., Ferraz, A. S. M., da Silva, T. E. O., & Marocolo, M. (2017). Effects of intermittent fasting and chronic swimming exercise on body composition and lipid metabolism. Applied Physiology, Nutrition & Metabolism, 42(12), 1341–1346.
• Yongin Cho, Namki Hong, Kyung-won Kim, Sung joon Cho, Minyoung Lee, Yeon-hee Lee, Byung-Wan Lee. (2019). The effectiveness of intermittent fasting to reduce body mass index and glucose metabolism: a systematic review and meta-analysis. Journal of Clinical Medicine, (10), 1645.
• Ahmed, A., Saeed, F., Arshad, M. U., Afzaal, M., Imran, A., Ali, S. W., Imran, M. (2018). Impact of intermittent fasting on human health: an extended review of metabolic cascades. International Journal of Food Properties, 21(1), 2700–2713.
• Lv, M. Zhu, X. Wang, H. Wang, F. Guan, W. (2014). Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis. PLoS One, 9(12), e115147. DOI: 10.1371/journal.pone.0115147.
• Jakubowicz, D. Barnea, M. Wainstein, J. Froy, O. (2013). High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity, 21, 2504–2512.

References Cont.

• Lamming D. W, Ye L, Sabatini D. M, Baur J. A. (2013). Rapalogs and mtor inhibitors as anti-aging therapeutics. J Clin Invest. 123(3):980–9.
• Saxton R. A, Sabatini D. M. (2017). mtor signaling in growth, metabolism, and disease. Cell. 169(2):361–71.
• Witbracht, M. Keim, N.L. Forester, S. Widaman, A. Laugero, K. (2015). Female breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure. Physiol. Behav. 140, 215–221.
• Bagherniya M, Butler A. E, Barreto G. E, Sahebkar A. (2018). The effect of fasting or calorie restriction on autophagy induction: a review of the literature. Ageing Res Rev. 47:183–97.
• Sabatini D. M. (2017). Twenty-five years of mtor: uncovering the link from nutrients to growth. Proc Natl Acad Sci U S A. 114(45):11818–25.
• Weichhart T. (2018). mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review. Gerontology. 64(2):127–34
• Mougios, V. (2006). Exercise biochemistry. Human Kinetics.
• Schübel, R., Nattenmüller, J., Sookthai, D., Nonnenmacher, T., Graf, M. E., Riedl, L., Kühn, T. (2018). Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: a randomized controlled trial. American Journal of Clinical Nutrition, 108(5), 933–945.

References Cont.

Qasrawi, S. O., Pandi-Perumal, S. R., & BaHammam, A. S. (2017). The effect of intermittent fasting during Ramadan on sleep, sleepiness, cognitive function, and circadian rhythm. Sleep and Breathing: International Journal of the Science and Practice of Sleep Medicine, 21(3), 577.

Antunes, Fernanda, Erustes, Adolfo Garcia, Costa, Angélica Jardim, Nascimento, Ana Carolina, Bincoletto, Claudia, Ureshino, Rodrigo Portes, Pereira, Gustavo José Silva, & Smaili, Soraya Soubhi. (2018). Autophagy and intermittent fasting: the connection for cancer therapy?. Clinics, 73(Suppl. 1), e814s.

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