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Written by Michael Rudoplh, Ph. D.
Intermittent Fasting
Lose Fat and Maintain Lean Body Mass
By Michael J. Rudolph, Ph.D.
Intermittent fasting has been shown to promote substantial fat loss while maintaining lean body mass when combined with resistance training. Subjects doing alternate-day fasting for three weeks lost 2.5% of their initial weight and 4% fat mass.
Like most good memes, old wives’ tales die hard, especially when they seem plausible and do no apparent harm. One of those sticky old wives’ tales I heard from my Mom throughout much of my childhood to persuade me and my two brothers to eat our breakfast was “breakfast gets the day’s work done.” I’m sure Mom had the best of intentions and was simply trying to get my two brothers and me to eat our healthy breakfast as we probably didn’t want to do anything except go outside to play. Now, I’m not saying my Mother was wrong, just inaccurate, especially considering a rash of recent scientific studies that show skipping breakfast, or even a few meals a day, every so often seems to distinctively promote enduring health benefits while also providing a terrific way to lose body fat. In fact, this dietary approach, known as intermittent fasting (IF), has become the latest diet craze. Yet, unlike many fads, IF is likely here to stay as science has uncovered several very important health benefits brought on by IF that are triggered by evolutionarily conserved, adaptive cellular responses that improve glucose regulation and bolster the body’s resistance to stress, while also suppressing inflammation throughout the body, altogether promoting health and wellness. IF has also been shown to promote substantial fat loss while uniquely maintaining lean body mass when combined with resistance training, unlike many hypocaloric diets that instead tend to promote the loss of body fat and muscle.
Different Fasting Approaches Provide Different Benefits
Three main IF protocols are currently employed. In “time-restricted feeding,” the individual only eats within a certain time window ranging from four to 12 hours throughout the day without trying to reduce caloric intake. Longer fasting protocols have also become quite popular, with one being alternate-day fasting where, as the name implies, the individual fasts completely every other day several times per week. Then there is the prolonged fasting method, which entails fasting for more than 48 hours.
Of the time-restricted protocols, the shortest restricted feeding window of four hours lowered inflammatory factors such as TNF-alpha and IL-6, indicating the capacity to reduce inflammation throughout the body.1,2 Inflammation is a normal process that can protect and heal the body following physical injury or infection. However, chronic inflammation is involved in a number of disease states. For instance, chronic inflammation in fat cells is closely related to the development of insulin resistance and type 2 diabetes. Interestingly, the four-hour feeding window also significantly increased glucose uptake into cells while also increasing other insulin action,3,4 suggesting the anti-inflammatory effect of four-hour time-restricted feeding contributes to improved insulin function.
The other time-restricting protocols of seven to eight5,6 and 10 to 12 hours7,8 also lowered and increased blood glucose in several studies, but had no impact on inflammatory markers or insulin function, implying longer feeding times preclude the anti-inflammatory impact of IF. Interestingly, the seven to eight and 10 to 12-hour time-restricted protocols promoted consistent weight loss ranging from 1% to 5% loss of bodyweight over four weeks, while the shortest four-hour feeding routine did not provide any weight loss, which was somewhat surprising as shorter feeding windows should reduce total caloric intake, promoting more weight loss.9 The potential reason for this unanticipated outcome is test subjects in these four-hour studies did time-restricted feeding every other day, permitting normal or even hypercaloric intake on off days that mitigate any possible weight loss. Moreover, time-restricted feeding studies done in mice showed the four-hour feeding window led to the most consistent weight loss relative to the other time feeding windows.
Alternate-day fasting and prolonged fasting protocols effectively improved multiple indicators of cardiovascular health including lowered cholesterol, triglycerides, and blood pressure while also reducing blood glucose and insulin resistance, suggesting an anti-inflammatory effect from both of these fasting routines as well.10-12 Each of these two fasting approaches also promoted extensive weight/fat loss as demonstrated in a study where subjects doing alternate-day fasting for three weeks lost 2.5% of their initial weight and 4% fat mass.13 Two additional trials involved overweight women assigned to either a prolonged fasting protocol where test subjects fasted for 48 hours straight per week, or underwent a more classic 25% reduction in daily caloric intake. Each group lost the same amount of weight during the six-month period. However, those in the prolonged fasting group had a larger reduction in waist circumference, which typically correlates with greater fat loss, suggesting alternate-day fasting caused more fat loss.14,15
Maintain Hard-Earned Muscle While Cutting Fat
Besides an effective way to burn body fat while vigorously promoting overall health, IF also seems to uniquely prevent muscle loss when combined with resistance training. In fact, several studies have shown muscle mass can be maintained16-19 while reducing body fat significantly when IF is done with resistance training. The maintenance of muscle mass is determined by changes in rates of muscle protein synthesis and skeletal muscle protein breakdown. Generally speaking, hypocaloric diets accelerate muscle protein breakdown while reducing muscle protein synthesis20,21, resulting in the loss of muscle mass. The muscle-sparing effect of IF plausibly occurs, in part, from the capacity of IF to improve insulin function in muscle tissue22, as the considerable reduction in fat brought on by IF potently decreases intramuscular fat stores.23 The decrease of fat within muscle tissue enhances the muscle cell’s response to the anabolic hormone insulin24, which drastically increases muscle protein synthesis25, likely contributing to the sparing of muscle loss while fasting. IF also precludes muscle loss by initiating the metabolic switch from glucose as a fuel source to the use of fatty acids instead, which generates much greater levels of ketones. These ketones tend to minimize muscle protein breakdown as they are a preferred energy source instead of protein-derived amino acids from muscle tissue.
Distinct Health Benefits of IF
IF protocols improving body composition have become quite popular, as this dietary approach undoubtedly encourages extensive fat loss while maintaining muscle mass. Science has also uncovered added health benefits brought on by IF that are not solely due to weight loss.26,27 This is because IF triggers adaptive metabolic and cellular processes that produce energy from divergent energy sources within the body in response to the more severe energy deficit brought on by IF. For starters, IF robustly activates a process known as autophagy. When the body has sufficient nutrients, autophagy simply degrades damaged cellular components, replacing them to maintain normal cell function. When IF starves the cell, autophagy kicks in to another gear, digesting some cell components that may not even be damaged, converting them into the necessary energy for survival. Animal studies have shown evidence of autophagy after 24 hours of fasting.28 There are, however, no conclusive human studies indicating an optimal period of fasting to achieve autophagy. Yet, fasting periods of 24 hours is a good place to start promoting autophagy.
IF also cranks up production of ketones considerably as, once again, IF engenders the most severe caloric deficit of any dietary protocol that depletes glucose levels in the body. After stored glucose is depleted within roughly the first 24 hours of fasting, the liver begins to break down fat into ketones for energy, ultimately boosting ketone levels in the body. Greater ketone levels and increased autophagy seem to provide parallel protection against such deadly diseases as cancer, as ketones negatively influence several anabolic growth factors that when overactive, support development of cancer29, while autophagy suppresses tumorigenesis by inhibiting cancer-cell survival via induced cell death.30
More ketones and enhanced autophagy also appear to improve immune system function, which will most certainly further improve overall health. Autophagy facilitates immune system function by degrading toxins and infectious agents using the same mechanisms it does to destroy damaged cellular components, while ketones have been shown to enhance function of a key part of the immune system known as T cells.31 Of course, once again, how much fasting is necessary to improve immune function has not been specifically identified just yet. So, keep an eye out for future reports on IF here in Muscular Development as we will surely provide this important information as it becomes available, seeing that IF appears to elicit some remarkable health benefits along with a leaner, more muscular physique.
For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biological effects of exercise as a fellow at Harvard Medical School and Columbia University. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK – leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a Senior Scientist working at the New York Structural Biology Center where he investigates the molecular nature of human illness and disease.
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References:
1. Sherman H, Frumin I et al. (2011) Long-term restricted feeding alters circadian expression and reduces the level of inflammatory and disease markers. J Cell Mol Med 15, 2745-2759.
2. Sherman H, Genzer Y et al. (2012) Timed high-fat diet resets circadian metabolism and prevents obesity. Faseb J 26, 3493-3502.
3. Halberg N, Henriksen M et al. (2005) Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985) 99, 2128-2136.
4. Soeters MR, Lammers NM et al. (2009) Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism. Am J Clin Nutr 90, 1244-1251.
5. Aksungar FB, Topkaya AE and Akyildiz M. (2007) Interleukin-6, C-reactive protein and biochemical parameters during prolonged intermittent fasting. Ann Nutr Metab 51, 88-95.
6. Temizhan A, Tandogan I et al. (2000) The effects of Ramadan fasting on blood lipid levels. Am J Med 109, 341-342.
7. LeCheminant JD, Christenson E et al. (2013) Restricting nighttime eating reduces daily energy intake in healthy young men: a short-term cross-over study. Br J Nutr 110, 2108-2113.
8. Adlouni A, Ghalim N et al. (1997) Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol. Ann Nutr Metab 41, 242-249.
9. Rothschild J, Hoddy KK et al. (2014) Time-restricted feeding and risk of metabolic disease: a review of human and animal studies. Nutr Rev 72, 308-318.
10. Fontana L, Meyer TE et al. (2004) Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 101, 6659-6663.
11. Most J, Gilmore LA et al. (2018) Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance. Am J Physiol Endocrinol Metab 314, E396-E405.
12. Lefevre M, Redman LM et al. (2009) Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 203, 206-213.
13. Heilbronn LK, Smith SR et al. (2005) Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr 81, 69-73.
14. Harvie MN, Pegington M et al. (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 (Lond) 35, 714-727.
15. Harvie M, Wright C et al. (2013) The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr 110, 1534-1547.
16. Tinsley GM, Forsse JS et al. (2017) Time-restricted feeding in young men performing resistance training: A randomized controlled trial. Eur J Sport Sci 17, 200-207.
17. Tinsley GM, Moore ML et al. (2019) Time-restricted feeding plus resistance training in active females: a randomized trial. Am J Clin Nutr 110, 628-640.
18. Trabelsi K, Stannard SR et al. (2013) Effect of fed- versus fasted state resistance training during Ramadan on body composition and selected metabolic parameters in bodybuilders. J Int Soc Sports Nutr 10, 23.
19. Trabelsi K, Stannard SR et al. (2013) Effect of resistance training during Ramadan on body composition and markers of renal function, metabolism, inflammation, and immunity in recreational bodybuilders. Int J Sport Nutr Exerc Metab 22, 267-275.
20. Carbone JW, McClung JP et al. (2019) Recent Advances in the Characterization of Skeletal Muscle and Whole-Body Protein Responses to Dietary Protein and Exercise during Negative Energy Balance. Adv Nutr 10, 70-79.
21. Rennie MJ, Edwards RH et al. (1982) Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clin Sci (Lond) 63, 519-523.
22. Keenan S, Cooke MB and Belski R. (2020) The Effects of Intermittent Fasting Combined with Resistance Training on Lean Body Mass: A Systematic Review of Human Studies. Nutrients 12.
23. van Loon LJ, Koopman R et al. (2003) Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state. J Physiol 553, 611-625.
24. Larson-Meyer DE, Newcomer BR and Hunter GR. (2002) Influence of endurance running and recovery diet on intramyocellular lipid content in women: a 1H NMR study. Am J Physiol Endocrinol Metab 282, E95-E106.
25. Hillier TA, Fryburg DA et al. (1998) Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis in the human forearm. Am J Physiol 274, E1067-1074.
26. Panda S. (2016) Circadian physiology of metabolism. Science 354, 1008-1015.
27. Longo VD and Mattson MP. (2014) Fasting: molecular mechanisms and clinical applications. Cell Metab 19, 181-192.
28. Cui J, Shi S et al. (2013) Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys. PLoS One 8, e69720.
29. Bielohuby M, Menhofer D et al. (2011) Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein. Am J Physiol Endocrinol Metab 300, E65-76.
30. Perez-Hernandez M, Arias A et al. Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization. Cancers (Basel) 11.
31. Hirschberger S, Strauss G et al. (2021) Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming. EMBO Mol Med 13, e14323.
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Intermittent Fasting
Lose Fat and Maintain Lean Body Mass
By Michael J. Rudolph, Ph.D.
Intermittent fasting has been shown to promote substantial fat loss while maintaining lean body mass when combined with resistance training. Subjects doing alternate-day fasting for three weeks lost 2.5% of their initial weight and 4% fat mass.
Like most good memes, old wives’ tales die hard, especially when they seem plausible and do no apparent harm. One of those sticky old wives’ tales I heard from my Mom throughout much of my childhood to persuade me and my two brothers to eat our breakfast was “breakfast gets the day’s work done.” I’m sure Mom had the best of intentions and was simply trying to get my two brothers and me to eat our healthy breakfast as we probably didn’t want to do anything except go outside to play. Now, I’m not saying my Mother was wrong, just inaccurate, especially considering a rash of recent scientific studies that show skipping breakfast, or even a few meals a day, every so often seems to distinctively promote enduring health benefits while also providing a terrific way to lose body fat. In fact, this dietary approach, known as intermittent fasting (IF), has become the latest diet craze. Yet, unlike many fads, IF is likely here to stay as science has uncovered several very important health benefits brought on by IF that are triggered by evolutionarily conserved, adaptive cellular responses that improve glucose regulation and bolster the body’s resistance to stress, while also suppressing inflammation throughout the body, altogether promoting health and wellness. IF has also been shown to promote substantial fat loss while uniquely maintaining lean body mass when combined with resistance training, unlike many hypocaloric diets that instead tend to promote the loss of body fat and muscle.
Different Fasting Approaches Provide Different Benefits
Three main IF protocols are currently employed. In “time-restricted feeding,” the individual only eats within a certain time window ranging from four to 12 hours throughout the day without trying to reduce caloric intake. Longer fasting protocols have also become quite popular, with one being alternate-day fasting where, as the name implies, the individual fasts completely every other day several times per week. Then there is the prolonged fasting method, which entails fasting for more than 48 hours.
Of the time-restricted protocols, the shortest restricted feeding window of four hours lowered inflammatory factors such as TNF-alpha and IL-6, indicating the capacity to reduce inflammation throughout the body.1,2 Inflammation is a normal process that can protect and heal the body following physical injury or infection. However, chronic inflammation is involved in a number of disease states. For instance, chronic inflammation in fat cells is closely related to the development of insulin resistance and type 2 diabetes. Interestingly, the four-hour feeding window also significantly increased glucose uptake into cells while also increasing other insulin action,3,4 suggesting the anti-inflammatory effect of four-hour time-restricted feeding contributes to improved insulin function.
The other time-restricting protocols of seven to eight5,6 and 10 to 12 hours7,8 also lowered and increased blood glucose in several studies, but had no impact on inflammatory markers or insulin function, implying longer feeding times preclude the anti-inflammatory impact of IF. Interestingly, the seven to eight and 10 to 12-hour time-restricted protocols promoted consistent weight loss ranging from 1% to 5% loss of bodyweight over four weeks, while the shortest four-hour feeding routine did not provide any weight loss, which was somewhat surprising as shorter feeding windows should reduce total caloric intake, promoting more weight loss.9 The potential reason for this unanticipated outcome is test subjects in these four-hour studies did time-restricted feeding every other day, permitting normal or even hypercaloric intake on off days that mitigate any possible weight loss. Moreover, time-restricted feeding studies done in mice showed the four-hour feeding window led to the most consistent weight loss relative to the other time feeding windows.
Alternate-day fasting and prolonged fasting protocols effectively improved multiple indicators of cardiovascular health including lowered cholesterol, triglycerides, and blood pressure while also reducing blood glucose and insulin resistance, suggesting an anti-inflammatory effect from both of these fasting routines as well.10-12 Each of these two fasting approaches also promoted extensive weight/fat loss as demonstrated in a study where subjects doing alternate-day fasting for three weeks lost 2.5% of their initial weight and 4% fat mass.13 Two additional trials involved overweight women assigned to either a prolonged fasting protocol where test subjects fasted for 48 hours straight per week, or underwent a more classic 25% reduction in daily caloric intake. Each group lost the same amount of weight during the six-month period. However, those in the prolonged fasting group had a larger reduction in waist circumference, which typically correlates with greater fat loss, suggesting alternate-day fasting caused more fat loss.14,15
Maintain Hard-Earned Muscle While Cutting Fat
Besides an effective way to burn body fat while vigorously promoting overall health, IF also seems to uniquely prevent muscle loss when combined with resistance training. In fact, several studies have shown muscle mass can be maintained16-19 while reducing body fat significantly when IF is done with resistance training. The maintenance of muscle mass is determined by changes in rates of muscle protein synthesis and skeletal muscle protein breakdown. Generally speaking, hypocaloric diets accelerate muscle protein breakdown while reducing muscle protein synthesis20,21, resulting in the loss of muscle mass. The muscle-sparing effect of IF plausibly occurs, in part, from the capacity of IF to improve insulin function in muscle tissue22, as the considerable reduction in fat brought on by IF potently decreases intramuscular fat stores.23 The decrease of fat within muscle tissue enhances the muscle cell’s response to the anabolic hormone insulin24, which drastically increases muscle protein synthesis25, likely contributing to the sparing of muscle loss while fasting. IF also precludes muscle loss by initiating the metabolic switch from glucose as a fuel source to the use of fatty acids instead, which generates much greater levels of ketones. These ketones tend to minimize muscle protein breakdown as they are a preferred energy source instead of protein-derived amino acids from muscle tissue.
Distinct Health Benefits of IF
IF protocols improving body composition have become quite popular, as this dietary approach undoubtedly encourages extensive fat loss while maintaining muscle mass. Science has also uncovered added health benefits brought on by IF that are not solely due to weight loss.26,27 This is because IF triggers adaptive metabolic and cellular processes that produce energy from divergent energy sources within the body in response to the more severe energy deficit brought on by IF. For starters, IF robustly activates a process known as autophagy. When the body has sufficient nutrients, autophagy simply degrades damaged cellular components, replacing them to maintain normal cell function. When IF starves the cell, autophagy kicks in to another gear, digesting some cell components that may not even be damaged, converting them into the necessary energy for survival. Animal studies have shown evidence of autophagy after 24 hours of fasting.28 There are, however, no conclusive human studies indicating an optimal period of fasting to achieve autophagy. Yet, fasting periods of 24 hours is a good place to start promoting autophagy.
IF also cranks up production of ketones considerably as, once again, IF engenders the most severe caloric deficit of any dietary protocol that depletes glucose levels in the body. After stored glucose is depleted within roughly the first 24 hours of fasting, the liver begins to break down fat into ketones for energy, ultimately boosting ketone levels in the body. Greater ketone levels and increased autophagy seem to provide parallel protection against such deadly diseases as cancer, as ketones negatively influence several anabolic growth factors that when overactive, support development of cancer29, while autophagy suppresses tumorigenesis by inhibiting cancer-cell survival via induced cell death.30
More ketones and enhanced autophagy also appear to improve immune system function, which will most certainly further improve overall health. Autophagy facilitates immune system function by degrading toxins and infectious agents using the same mechanisms it does to destroy damaged cellular components, while ketones have been shown to enhance function of a key part of the immune system known as T cells.31 Of course, once again, how much fasting is necessary to improve immune function has not been specifically identified just yet. So, keep an eye out for future reports on IF here in Muscular Development as we will surely provide this important information as it becomes available, seeing that IF appears to elicit some remarkable health benefits along with a leaner, more muscular physique.
For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biological effects of exercise as a fellow at Harvard Medical School and Columbia University. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK – leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a Senior Scientist working at the New York Structural Biology Center where he investigates the molecular nature of human illness and disease.
DISCUSS ON OUR FORUMS
SUBSCRIBE TO MD TODAY
GET OFFICIAL MD STUFF
VISIT OUR STORE
ALSO, MAKE SURE TO FOLLOW US ON:
YOUTUBE
References:
1. Sherman H, Frumin I et al. (2011) Long-term restricted feeding alters circadian expression and reduces the level of inflammatory and disease markers. J Cell Mol Med 15, 2745-2759.
2. Sherman H, Genzer Y et al. (2012) Timed high-fat diet resets circadian metabolism and prevents obesity. Faseb J 26, 3493-3502.
3. Halberg N, Henriksen M et al. (2005) Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985) 99, 2128-2136.
4. Soeters MR, Lammers NM et al. (2009) Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism. Am J Clin Nutr 90, 1244-1251.
5. Aksungar FB, Topkaya AE and Akyildiz M. (2007) Interleukin-6, C-reactive protein and biochemical parameters during prolonged intermittent fasting. Ann Nutr Metab 51, 88-95.
6. Temizhan A, Tandogan I et al. (2000) The effects of Ramadan fasting on blood lipid levels. Am J Med 109, 341-342.
7. LeCheminant JD, Christenson E et al. (2013) Restricting nighttime eating reduces daily energy intake in healthy young men: a short-term cross-over study. Br J Nutr 110, 2108-2113.
8. Adlouni A, Ghalim N et al. (1997) Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol. Ann Nutr Metab 41, 242-249.
9. Rothschild J, Hoddy KK et al. (2014) Time-restricted feeding and risk of metabolic disease: a review of human and animal studies. Nutr Rev 72, 308-318.
10. Fontana L, Meyer TE et al. (2004) Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 101, 6659-6663.
11. Most J, Gilmore LA et al. (2018) Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance. Am J Physiol Endocrinol Metab 314, E396-E405.
12. Lefevre M, Redman LM et al. (2009) Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 203, 206-213.
13. Heilbronn LK, Smith SR et al. (2005) Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr 81, 69-73.
14. Harvie MN, Pegington M et al. (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 (Lond) 35, 714-727.
15. Harvie M, Wright C et al. (2013) The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr 110, 1534-1547.
16. Tinsley GM, Forsse JS et al. (2017) Time-restricted feeding in young men performing resistance training: A randomized controlled trial. Eur J Sport Sci 17, 200-207.
17. Tinsley GM, Moore ML et al. (2019) Time-restricted feeding plus resistance training in active females: a randomized trial. Am J Clin Nutr 110, 628-640.
18. Trabelsi K, Stannard SR et al. (2013) Effect of fed- versus fasted state resistance training during Ramadan on body composition and selected metabolic parameters in bodybuilders. J Int Soc Sports Nutr 10, 23.
19. Trabelsi K, Stannard SR et al. (2013) Effect of resistance training during Ramadan on body composition and markers of renal function, metabolism, inflammation, and immunity in recreational bodybuilders. Int J Sport Nutr Exerc Metab 22, 267-275.
20. Carbone JW, McClung JP et al. (2019) Recent Advances in the Characterization of Skeletal Muscle and Whole-Body Protein Responses to Dietary Protein and Exercise during Negative Energy Balance. Adv Nutr 10, 70-79.
21. Rennie MJ, Edwards RH et al. (1982) Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clin Sci (Lond) 63, 519-523.
22. Keenan S, Cooke MB and Belski R. (2020) The Effects of Intermittent Fasting Combined with Resistance Training on Lean Body Mass: A Systematic Review of Human Studies. Nutrients 12.
23. van Loon LJ, Koopman R et al. (2003) Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state. J Physiol 553, 611-625.
24. Larson-Meyer DE, Newcomer BR and Hunter GR. (2002) Influence of endurance running and recovery diet on intramyocellular lipid content in women: a 1H NMR study. Am J Physiol Endocrinol Metab 282, E95-E106.
25. Hillier TA, Fryburg DA et al. (1998) Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis in the human forearm. Am J Physiol 274, E1067-1074.
26. Panda S. (2016) Circadian physiology of metabolism. Science 354, 1008-1015.
27. Longo VD and Mattson MP. (2014) Fasting: molecular mechanisms and clinical applications. Cell Metab 19, 181-192.
28. Cui J, Shi S et al. (2013) Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys. PLoS One 8, e69720.
29. Bielohuby M, Menhofer D et al. (2011) Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein. Am J Physiol Endocrinol Metab 300, E65-76.
30. Perez-Hernandez M, Arias A et al. Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization. Cancers (Basel) 11.
31. Hirschberger S, Strauss G et al. (2021) Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming. EMBO Mol Med 13, e14323.
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