Ultimate Guide to Intermittent Fasting IV – What The Research Says
Interested in Intermittent Fasting? Grab my book on it here: Feast.Fast.Fit. – Train Your Body to Torch Fat, Build Muscle, and Never Diet Again
What the Research Says: One of the first things someone unknown to fasting will throw at you is that it leads to muscle loss. Next they’ll tell you that your metabolism will slow down and you’ll just magically get fat. Does this hold weight? Martin Berkhan provides a lot of information about this on his site but I will summarize one of the noteworthy studies.
In the study, “Leucine, glucose, and energy metabolism after 3 days of fasting in healthy human subjects,” the researchers didn’t see a decrease in metabolism during fasting until 60 hours into the fast . Even then, the decrease was only about 8% . Other studies found that during shorter term fasts (36-48 hours) there was an increase in metabolic rate (from 3-10%)  .
Even if a fast led to a short term decrease in metabolic rate, anytime you diet or restrict energy, your metabolism slows. The body does this to try and conserve energy since you are limiting energy intake. Knowing that, would you say to somebody, “oh don’t diet, it will just lower your metabolism?” I hope not, human metabolism is much more complex than that. Chronically fasting, just like chronically limiting nutrients, isn’t the best option either though. Again, it’s about finding balance.
Fasting for Muscle?
In terms of muscle loss, the study, “Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss,” found that an intermittent fasting diet lead to more lean mass being retained vs. a diet of daily calorie restriction.  Studies on Ramadan also show that fat free mass is retained quite well in regards to fasting.
There’s always two sides to every argument and then there’s a truth right in the middle. Opponents of fasting often claim that “intermittent fasting” leads to catabolism which then automatically leads to muscle loss. But hold on a minute. First off, the definition of catabolism is not necessarily muscle loss, even though that’s the only context you see it in. Catabolism refers to certain molecules being broken down to provide energy. Protein isn’t the only thing that’s available to be used here but so are lipids (fats) and polysaccharides. This is a completely normal process and it’s a necessity for our bodies.
Autophagy is a word I threw out early so what exactly is it? Put simply, autophagy means “self – eating”, as auto means self in Greek and phagy is abbreviated for eating. It is a catabolic process that helps rid the body of unneeded and possibly dysfunctional cellular debris. So why does this happen?
Remember, hundreds of years ago food wasn’t as accessible as it is today. Our body needed ways to cope with stretches of no food intake. As more time passes with no food, your cells will start to eat or digest themselves. Don’t panic, this is actually healthy and normal (within reason). Your cells can actually use old proteins to recycle and release amino acids out into your bloodstream .
Autophagy is initiated when the cell is starved and lacking nutrients or even under normal conditions when the body needs to remove damaged proteins and organelles in response to possible cell damage . It can also occur due to physiological stimuli like certain hormones and growth factors or even pathogens . There seems to be a potential link between autophagy and disease which makes sense given the research that is emerging about so many diseases potentially being metabolic in nature. But let’s get back to things that are more important, like muscle building and fat loss….(sarcasm).
Right now you’re probably thinking, “A catabolic process where my body is starving and eating itself, my poor muscle has no chance.” Wrong. Although most of the attention autophagy garners is due to its beneficial health and anti-aging effects; it actually helps preserve muscle mass. I will leave you with some quotes from two interesting studies on autophagy and muscle.
- “Autophagy inhibition exacerbated muscle loss during denervation and fasting. Thus, autophagy flux is important to preserve muscle mass and to maintain myofiber integrity.” 
- “Moreover, autophagy inhibition does not protect skeletal muscles from atrophy during denervation and fasting, but instead promotes greater muscle loss. In conclusion, autophagy plays a critical role for myofiber maintenance and its activation is crucial to avoid accumulation of toxic proteins and dysfunctional organelles that, in the end, would lead to atrophy and weakness.” 
This is just further evidence that you do not need to lose sleep over muscle loss in short periods of fasting as your body has plenty of mechanisms to keep what it deems as important!
A lot of the benefits of fasting are due to allowing our body to clean itself out from the 20th century, eat until you can’t breathe lifestyle. A fast is the only true detox out there. So it’s painful watching people throw thousands in the trash to buy scam detox and cleanse products that promise miracles and leave you with nothing but less money and dignity. Hopefully by now you can appreciate some of the beneficial effects of catabolic processes that occur during periods of fasting.
What Does The Research Say?
Here are some studies that helped to shape my views on Intermittent Fasting. I’ve compiled a few different studies that cover intermittent fasting, alternate day fasting, fasted exercise and calorie restriction (CR). I’ve highlighted some main ideas I thought were interesting and useful from each study.
- “Effect of intermittent fasting and refeeding on insulin action in healthy men.” Nils Halberg (2005).
This study invested 8 young healthy men with normal BMI levels to an intermittent fasting regiment. Every other day they fasted for 20 hours, for 15 days. The researchers investigate the “theory of thrifty genes” which suggests that the fluctuations between feast and famine are necessary for optimal metabolic function. I happen to agree with them there.
Some interesting findings and quotes from this study include:
- Insulin-mediated whole body glucose uptake rates increased
- Increase in plasma adiponectin levels
- “This is the first study in humans in which increased insulin action on whole body glucose uptake and adipose tissue lipolysis has been obtained by means of intermittent fasting”
- “The findings that intermittent fasting increases insulin sensitivity on the whole body level as well as in adipose tissue support the view that cycles of feast and famine are important as an initiator of thrifty genes leading to improvements in metabolic function. We suggest that afasting-induced increase in circulating adiponectin is at least partly responsible for this finding. The change in adiponectin, together with changes in plasma leptin with fasting, underlines the important role of the adipose tissue in recognizing the oscillation in energy stores. “
- One day of food restriction does not result in an increase in subsequent daily food intake in humans. David Levitsky (2010).
There are some who worry that if they go a few hours without food, they will significantly overeat. Unfortunately, for some, this can happen. Others experience quite the opposite, and a fast can help control their hunger. This is why dieting is so individual.
In this study, the researchers examined how one day of food restriction would affect the participants and their food intake in the subsequent days. For four weeks, using all prepared meals, 22 women were fed Monday through Friday. The first week they all ate the same, then on every Monday there were three groups, 1.) ate ad libitum, 2.) ate 1,200 calories, 3.) fasted. Then from Tuesday to Friday they went back to eating ad libitum. What they found was that even after the 24 hour fast there was not an increase in spontaneous food intake amongst the fasted group.
In closing the author’s state, “to sustain weight loss, it is necessary to continually reduce energy intake, perhaps regularly interspersing a day of fasting or food restriction within their weekly food cycle may allow people to maintain their reduced intake and thereby produce a sustained reduction in body weight.”
- “Ramadan and Its Effect on Fuel Selection during Exercise and Following Exercise Training” Stephen R. Stannard.
A lot of fasting research comes from studies done on those who participate in Ramadan. The only issue with this type of fasting is the restriction of water or any fluids during their fast. I don’t generally recommend this as dehydration during this period can negatively impact growth hormone release, which is one of the adaptations we are after during a fast.
This study was interested in exploring the short-term physiological adaptations during fasting, one example is the sparing of carbohydrate stores and mobilizing of fats (lipids) to provide fuel for the body. The fast and then reefed model has shown potential in improving the body’s ability to utilize fats for energy.
Some of the interesting quotes from the study include:
- “Short term fasting regularly exposes active tissue to periods of increased lipid (fat) availability and utilization”
- “The results of this study indicate that endurance training undertaken without breaking the overnight fast leads to an increased capacity of the trained muscle to utilize lipid and also store glycogen in the fed state”
- “There is strong evidence that participation in Ramadan promotes the ability of the body to better utilize lipid at rest and during exercise.”
Hard not to be excited by some of the findings in this particular study. Increased resting glycogen stores and an increased ability to burn your undoubtedly excess fat for energy are useful tools for improving your physique and performance.
- “The effect on health of alternate day calorie restriction: Eating less and more than needed on alternate days prolongs life.” Johnson JB, Laub DR, John S.
The title of this was enough to intrigue me. This study was done on older patients (65+) and featured a modified alternate day fast. The eating pattern was ad lib on one day and then eating 20-50% of the estimated daily calories the following day. After monitoring this for 2.5 years the authors found: Improvement in a variety of disease conditions including insulin resistance, asthma, autoimmune disease, osteoarthritis, menopause related hot flashes, and more. What they conclude was that this style of eating was helpful in weight control, aids in prolonging lifespan and improves health.
- “Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake” Michael Anson, Zhihong Guo, Rafael de Cabo.
As I discussed earlier, caloric restriction is a fairly well established and accepted modality for increasing general health (increased insulin sensitivity, stress resistance, reduced morbidity). However, intermittent fasting:
- “Resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to exciotoxic stress.”
- “Dietary restriction or caloric restriction reduces cancer formation and kidney disease and increases the resistance of neurons to dysfunction and degeneration in experimental models of Alzheimer’s and Parkinson’s diseases as well as stroke.”
- “Fasting is known to result in an increased production of ketone bodies…known to provide some protective benefits to epileptic seizures”
- “Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice” KA J. Varaday
Although this is a study done on mice, there is a lot of interesting reading involved. The main purpose of the study was to determine how modified alternate day fasting effects adipocyte size, changes in body weight and triglyceride metabolism. Some of the interesting findings:
- Alternate day fasting effects adipocyte physiology
- Fat cell size was reduced
- Lipolysis was stimulated
- Reducing fat cell size positively effects insulin sensitivity
- “The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women.” Harvie, C. Wright, M. Pegington.
This was a study done on overweight women that were broken up into three groups. The women were exposed to either a.) An overall 25% energy restriction of intermittent energy and carbohydrate restriction (<40g), b.) A 25% energy restriction alone, and c.) A 25% energy restriction with intermittent energy and carbohydrate restriction + ad libitum protein and fat.
The authors found:
- “Insulin resistance reduced with the two intermittent and energy restriction diets”
- “Both intermittent energy and carbohydrate restriction diets had greater reductions in body fat compared with the energy restriction only diet”.
- “In the short term, intermittent energy and carbohydrate restriction is superior to daily energy restriction with respect to improved insulin sensitivity and body fat reduction.”
- “Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss?” Ka Varady.
This particular study looked at alternate day fasting vs. caloric restriction (15-60% reduction in usual calorie intake) in terms of weight loss. They refer to the alternate day fast as “Intermittent CR”, and it involved 24 hours of ad libitum food consumption followed by 24 hours of complete or partial food restriction. The full study has a ton of great discussion which I recommend reading.
After 3 and 12 weeks, there was similar weight loss and fat mass loss between the daily caloric restriction vs. intermittent CR (or modified alternate day fast). However, “less fat free mass was lost in response to the intermittent CR vs. caloric restriction alone.”
- “Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans” K De Bock, E. A Richter, A. P Russell.
This is another study done on fasted exercise (endurance) vs. fed exercise. Seeing as though the protocol outlined in the e-book features fasted cardio, it’s a good fit. There is a ton of great discussion in this study and I’m just going to cover the highlights but I recommend reading the whole thing.
There were 9 young healthy participants who participated in two exercise conditions (fed vs. fasted) over the course of 3 weeks for each. For one condition they performed endurance exercise after an overnight fast and the other featured exercise where carbohydrates were ingested before and during (intra-workout). The study was designed to compare how the fed vs. fasted conditions effect intramyocelluar triglyceride (IMTG or intramuscular fat) and glycogen content of muscle. Some of what the found is:
- IMTG breakdown was increased in fasted state
- Exercise in the carbohydrate fed state did not cause IMTG content to decrease
- Glucose ingestion during exercise increased insulin and decreased adrenaline which blunted HSL activity. HSL is hormone sensitive lipase and it works to break down triglycerides.
- Rate of muscle glycogen resynthesis (or regeneration of glycogen), during 4 hours post-exercise, was 3-fold higher after the fasted exercise vs. fed. This essentially means after fasted exercise insulin sensitivity is greatly increased compared to fed.
- “Beneficial metabolic adaptations due to endurance exercise in the fasted state.” Karen Van Proeyen, Karolina Szlufcik, Henri Nielens.
This is another recent study that explores the adaptations that occur during fasted exercise. Some of the noteworthy findings include:
- After a 6 week training period there was a 22% increase in basal glycogen content in fasted group and no change in the carbohydrate group.
- The fasted group enhanced the contribution of intramyocellular lipids (IMCL) to energy provision more than the carbohydrate group.
- Fasted exercise prevented a drop in blood glucose concentration but not in the carbohydrate group.
- “Alternate day fasting with high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet” Klempel MC, Kroeger CM, Varady KA (2012).
This study featured 32 obese subjects who either followed an alternate day fast of high fat (45%) and a group of low fat (25%) ADF. They started with a 2 week maintainence plan and then 8 week weight loss period using ADF. Here’s what they found:
- Bodyweight reduced in both groups
- Fat mass decreased in both, fat free mass stayed the same
- Waist circumference and LDL both decreased
- A high fat alternate day fast is equally as effective as a low fat alternate fast in losing weight and improving CHD risk factors.
Intermittent fasting is not a diet, it is a tool. You can use it to your betterment or detriment; the application is key. In working with thousands of clients, I cannot think of any who didn’t end up enjoying and regularly implementing fasting. I have also had tremendous success using it to improve blood markers of those with diabetes, metabolic syndrome and obesity. I believe it’s more than clear that IF can be used safely and effectively to improve one’s health and body composition.
I wrote this resource for clarity on a subject muddled with contradictions. While psuedo-scientific nutrition is “in” right now, this is another reminder that sometimes you need to back up and see the forest for the trees. Nothing is as black as white as the message fed to you by diet books or TV infomercials. Think for yourself and find what works best for YOU.
So what do you think? Have I intrigued you enough to at least try fasting once? If for nothing else, I hope you learned some new information about the human body and your metabolism. I appreciate you taking the time to read through this series and if you have any questions please post below.
 Nair, KS, and Sl Welle. “Leucine, Glucose, and Energy Metabolism after 3 Days of Fasting in Healthy Human Subjects.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web.
 Mansell, Pl, and IW Fellows. “Enhanced Thermogenic Response to Epinephrine after 48-h Starvation in Humans.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web.
 Zauner, C., and A. Kranz. “Resting Energy Expenditure in Short-term Starvation Is Increased as a Result of an Increase in Serum Norepinephrine.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web.
 Varady, KA. “Intermittent versus Daily Calorie Restriction: Which Diet Regimen Is More Effective for Weight Loss?” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web.
 Castro-Obregon, Susana. “The Discovery of Lysosomes and Autophagy.”Nature.com. Nature Publishing Group, n.d. Web.
 Masiero, E., and L. Agatea. “Autophagy Is Required to Maintain Muscle Mass.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web.
 Masiero, E., and M. Sandri. “Autophagy Inhibition Induces Atrophy and Myopathy in Adult Skeletal Muscles.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web