Should I Try Intermittent Fasting?

What is Intermittent Fasting (IF)?

This is a popular term for several different diet plans. Each one is made up of windows of feeding and windows of fasting. For example, one of the most popular IF schedules is to eat between 12pm and 8pm and fast for the remaining 16 hours of the day. Some people choose to eat during a smaller or larger window or during different times of the day. Another popular way to implement intermittent fasting is to have two days per week where you fast or eat very few calories while eating normally the remaining 5 days.

You could also choose to try a longer fast. Some people fast for a week, a month, or more. The longest fast on record is from 1973. A 27-year-old man fasted for 382 days. He lived on nothing but water, tea, coffee, and nutritional supplements and went from 456 to 180 pounds (AND he only regained about 15 pounds after 5 years). However, professionals monitored his health closely and made sure he stayed healthy. Keep in mind that many people have died, often from heart failure, after fasting for as little as a month.

The Claim

Intermittent fasting is a good idea because it will help you burn body fat without constantly feeling hungry, keep metabolism high, and repair/prevent disease.

Initial Google Search

In order to understand why some experts think IF is the best diet plan, you need to know how the body stores energy. When you eat, your insulin increases and remains high for 3-5 hours during digestion. During this time, some of the food energy is used up by cells right away, some of it is stored as glycogen in the liver or muscles, and some of it is stored as body fat. The liver and muscles can’t store very much glycogen (only around 2,000 calories), but the body can store unlimited amounts of fat.

When you stop eating, your body turns primarily to the stored glycogen in your liver to keep itself going. Typically, after 3-5 hours, your insulin drops and you get hungry and eat again. The process starts over. Some experts believe that by eating every 3-5 hours, your body never gets a chance to use any of its body fat. You only burn easy-to-access glucose (made from the glycogen stored in the liver).

During my online research, I’ve seen many different ideas on when the body burns glycogen versus when it burns fat stores. Some experts believe no body fat is actually burned until you’ve been fasting for at least 48 hours and are in ketosis (My blog on the ketogenic diet is next in queue. Hold your horses). Other sources say the body starts burning fat just after you’ve finished digesting the previous meal and insulin levels have dropped (around 4 hours after eating). Some sources say the body is always burning both glucose and fat, but the ratio varies based on when you’ve last eaten and your activity level. Still other sources say that you burn fat while you’re sleeping even if your glycogen stores are full. Seriously, how is there no consensus on this?

Sources also vary as to whether or not your body will turn to muscle for fuel after it’s used the glycogen in the liver. Some are convinced this happens immediately after glycogen is depleted while others say this is very rare.

The idea behind fasting is that your body will finally get the chance to rely on stored body fat for fuel rather than glycogen from the liver or muscles.

Of course, the most commonly accepted weight loss method is calorie restriction. When you eat fewer calories, you lose weight. However, as we all know, it’s not quite that simple. Proponents of intermittent fasting are quick to point out that when someone starts dieting, they first lose glycogen stores, which contain several pounds of water. They say that actual fat loss won’t begin until glycogen is depleted.

Additionally, they cite a well-accepted phenomenon known as “adaptive thermogenesis”. This, put simply, is when the body learns to function with fewer calories per day. It’s also known as “decreased metabolism” or more recently, “The Biggest Loser Effect” (Former Biggest Loser contestants say they have to keep their caloric intake restricted to under 1000 calories a day in order to maintain their weights). This adaptive effect is thought to be irreversible. The effect is somewhat proportional to how extremely a person has dieted, but experts disagree on how much a person’s metabolic rate can really drop. Many experts acknowledge a 10-15% drop in metabolic rate, while others put that number closer to 40-50%.

One of the purported benefits of intermittent fasting is that it helps you burn fat while keeping the metabolism high. Some doctors say you will lose fat even if you continue to eat the same number of calories as before. Others say that you still need to decrease your overall calorie intake to lose fat, but, even when you stop fasting, your metabolism will still be as high as other same-weight people.

Here are the main claims made by IF supporters (most of these benefits are said to be attainable by fasting 12-24 hours at a time, depending on the source):

1. Fat loss: Insulin levels remain low, making stores of body fat accessible which leads to fat loss
2. Increased metabolism: Your metabolic rate will remain constant or even increase
3. Autophagy: The body will get rid of old/damaged cells or cell parts when there is limited energy to keep them running. This is supposed to improve the body’s ability to heal itself from long-term injury and may even help prevent cancer and Alzheimer’s Disease by getting rid of damaged cells and protein buildup.
4. Growth hormone: human growth hormone increases by up to 5 times. This prevents muscle breakdown and helps build new, healthy cells.
5. Increases lifespan: It is well documented that calorie restriction increases lifespan. This may be true for IF as well. This is thought to work by changing “gene expression” which means fewer signs of aging and age-related diseases.
6. Decreased hunger hormone: Ghrelin, the hunger hormone, tends to show up at times we are accustomed to eating. If you get your body used to eating in a smaller window, you will stop feeling hungry during other times. If you fast for more than a couple days, ghrelin will disappear.

Follow-up Questions:

1. How true are the claims above?
2. Can you lose fat while eating on a normal schedule (every 3-5 hours for 16 hours out of the day)? If so, how likely are you to end up with a slower metabolism?
3. Does your body really need to deplete all of its glycogen before it can start burning body fat? If so, how is it possible that people on low-fat diets (think vegans) are able to lose fat?
4. Does autophagy ever occur when you are not fasting?
5. I’ve heard most of the research supporting IF has been done on mice. Do human studies show the same results?

Peer Reviewed Research (Click here to skip to analysis)

1.Effects of intermittent fasting on body composition and clinical health markers in humans. (2015) https://www.ncbi.nlm.nih.gov/pubmed/26374764

This review analyzed several different studies that looked at different types of intermittent fasting. They found that alternate day fasting resulted in improvements in body weight, body fat, total cholesterol, triglycerides, and blood lipids. However, results were modest. People lost only 3-9% of their body weight after 3 to 24 weeks. This is does not seem to be any better than any other kind of diet. Additionally, researchers stated that results on time-restricted feeding were limited and inconclusive. No comments were made about metabolism changes or autophagy.

2. Health effects of intermittent fasting: hormesis or harm? A systematic review. (2015) https://www.ncbi.nlm.nih.gov/pubmed/26135345

This review found three randomized controlled trials and two observational studies that met criteria. All 5 studies found modest improvements in body weight and other metabolic risk factors. The authors concluded that the current literature supports intermittent fasting, but that much more research in humans is needed before the use of fasting as a health intervention can be recommended. Again, this study did not address the questions of metabolism changes or autophagy.

3. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings. (2014) https://www.ncbi.nlm.nih.gov/pubmed/24993615

This review wanted to compare IF to traditional calorie restricted diets to determine which approach would be better for decreasing type 2 diabetes risk factors. The researchers found similar improvements between the two types of diets in visceral fat mass, fasting insulin, and insulin resistance. They found that traditional calorie restricted diets were better for decreasing body weight than IF.

4. INTERMITTENT FASTING AND HUMAN METABOLIC HEALTH (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516560/

This review analyzed 13 other studies which used different types of intermittent fasting. Their goal was to make suggestions for where to go next with the research. Some of the conclusions they drew from analyzing the studies were:

All fasting protocols resulted in modest clinically significant weight loss and none seemed to do any physical or mental harm.

There is significant rodent data supporting time-restricted feeding, but these studies have not been replicated in humans

IF has not been shown to be superior to calorie restricted diets in any way

There are little or no published data linking IF with reduced incidences of diabetes, heart disease, cancer, Alzheimer’s disease or other chronic diseases.

5. Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism. (2015) https://www.ncbi.nlm.nih.gov/pubmed/25546413

This study looked at whether IF (alternate day fasting) would act on the same pathways as calorie restriction in order to extend life span and ameliorate age-related diseases. The study was 6 weeks long and anti-oxidant supplements were used for 3 of the 6 weeks. Their results showed mild increases in certain gene expressions associated with longevity, but most of these did not reach clinical significance.

6. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury. (2015) https://www.ncbi.nlm.nih.gov/pubmed/26103523

This is a mouse study which shows that IF induces autophagy in the heart.

7. 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. (2014) https://www.ncbi.nlm.nih.gov/pubmed/25502434

This is a review of 59 different mouse studies. Calorie restriction and ketogenic diet were found to “play an anti-cancer role” in 90% of the relevant studies. Only 60% of the studies looking at IF found a similar anti-cancer role. Researchers concluded that calorie restriction and ketogenic diets are better at fighting cancer than intermittent fasting.

8. Chronic intermittent fasting improves cognitive functions and brain structures in mice. (2013) https://www.ncbi.nlm.nih.gov/pubmed/23755298

This is a mouse study that found that IF mice had better learning and memory than control mice.

9. Fasting: molecular mechanisms and clinical applications. (2014) https://www.ncbi.nlm.nih.gov/pubmed/24440038

This is a summary of bacteria, rodent, and human studies. It states that IF results in: reduced oxidative damage and inflammation, optimized energy metabolism, and protection from diabetes, cancer, heart disease and neurodegeneration. It states that in humans, IF has been shown to reduce obesity, hypertension, asthma, and rheumatoid arthritis.

10. Effects of intermittent fasting on metabolism in men. (1992) https://www.ncbi.nlm.nih.gov/pubmed/23582559

This article reviewed older literature on IF. It states that animal models showed positive changes in glucose and lipid metabolism. In humans, it has shown a decrease in inflammation, lower oxidative stress, and better adherence than traditional diets.

11. Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials. (2015) https://www.ncbi.nlm.nih.gov/pubmed/26384657

This review looked at studies that compared calorie restriction diets to IF diets. Their main goal was to see whether IF diets were better at keeping metabolism high like they claim. They concluded that IF diets “do not appear to attenuate adaptive responses to energy restriction or improve weight loss efficiency” and that they work, but are not superior to calorie-restricted diets.

12. Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice. (2015) https://www.ncbi.nlm.nih.gov/pubmed/25645620

This is a mouse study that used mice that were predisposed to developing diabetes. One group of mice was fed a 10% calorie restricted diet, one was fed with alternate day IF, and one group was fed a regular control diet. None of the mice on calorie restriction of IF developed diabetes while 43% of the control group did.

13. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. (2012) https://www.ncbi.nlm.nih.gov/pubmed/23171320

This study found that IF plus calorie restriction is an effective weight loss strategy and that it words slightly better with a liquid diet.

14. Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent Fasting on Cognitive Performance at Rest and During Exercise in Adults. (2016) https://www.ncbi.nlm.nih.gov/pubmed/26438184

This study provided data showing that fasting during daylight hours may impair cognitive function and memory. This was not found with calorie-restricted diets.

15. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects. (2012) https://www.ncbi.nlm.nih.gov/pubmed/23244540

This study found that Ramadan-style fasting reduced overall inflammation. Researchers did not compare results to a control group or a calorie-restricted group.

16. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice. (2014) https://www.ncbi.nlm.nih.gov/pubmed/24176004

This study compared mice that were prone to heart disease with wild-type mice. Each type of mouse was fed with alternate day fasting, which resulted in an overall 20% decrease in calories. Each group also had control mice, which were fed a normal diet. In the wild mice, IF reduced markers of heart disease. However, in the mice that were heart-disease prone, markers of heart disease increased by as much as 3 times. Researchers concluded that alternate day fasting is not beneficial for mice with hypercholesterolemia.

17. Intermittent fasting: a “new” historical strategy for controlling seizures? (2013) https://www.ncbi.nlm.nih.gov/pubmed/23206889

This study is based on the idea that ketogenic diets can help children with epilepsy. Researchers thought IF may help in a similar way. In 4 out of 6 children studied, “transient improvements” were seen in seizure control with some “hunger-related adverse reactions”.

18. Fasting therapy for treating and preventing disease – current state of evidence. (2013) https://www.ncbi.nlm.nih.gov/pubmed/24434759

This review goes over the benefits of fasting that have been observed in research. The author states IF can help improve: rheumatic diseases, chronic pain syndromes, hypertension, metabolic syndrome, and possibly cancer. He states that deceleration or prevention of most chronic degenerative and chronic inflammatory diseases can be achieved through IF or traditional calorie restriction. He goes over possible mechanisms for these health benefits including promotion of autophagy and decreased oxidative stress.

19. Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis. (2013)https://www.ncbi.nlm.nih.gov/pubmed/23382817

This study discussed how IF caused infertility in rats and how this could apply to humans.

20. Impact of intermittent fasting on glucose homeostasis. (2016) https://www.ncbi.nlm.nih.gov/pubmed/27137896

This review looked at 4 case studies of fasting and found no improvements in blood glucose.

21. Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence. (2016) https://www.ncbi.nlm.nih.gov/pubmed/27422504

This review confirms that calorie restriction helps reduce cancer rates in animal and human studies. Researchers tried to determine whether IF would reduce cancer rates even further. Some mice studies show that it does. They confirmed that some studies show that IF leads to greater improvements in insulin sensitivity than calorie restriction. However, the authors thought the evidence was not strong enough to recommend the use of IF over calorie restriction.

22. Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism. (2009) https://www.ncbi.nlm.nih.gov/pubmed/19776143

This study compared a small number of people who were on an IF diet with a small group on a “standard diet”. After 2 weeks, no differences were noted between the 2 groups in terms of body weight, blood glucose, or insulin sensitivity. They did note a decrease in metabolism during rest in the IF group which they concluded might lead to weight gain.

23. Metabolic Effects of Intermittent Fasting. (2017) https://www.ncbi.nlm.nih.gov/pubmed/28715993

This article summarized the health benefits of IF supported by literature. They state that IF promotes weight loss and may improve metabolic health. They concluded that IF may be beneficial to improving health in the general population. They did not compare IF with traditional calorie restriction.

24. Comparison of High-Protein, Intermittent Fasting Low-Calorie Diet and Heart Healthy Diet for Vascular Health of the Obese. (2016) https://www.ncbi.nlm.nih.gov/pubmed/27621707

This study tested 40 obese adults. They were all put on a high-protein, low calorie IF diet for 12 weeks. Then half of them stayed on a maintenance IF diet while the other half was put on a maintenance “heart healthy” diet for a year. The IF group had less weight regain and better “arterial compliance” at the end of the year than the group on the heart healthy diet.

25. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. (2015) https://www.ncbi.nlm.nih.gov/pubmed/26529255

This study found that IF is useful for reducing inflammation in obese patients. They acknowledged that calorie-restricted diets do the same.

26. The effect of fasting on indicators of muscle damage. (2013) https://www.ncbi.nlm.nih.gov/pubmed/23266375

This study tested 29 participants after strength training. Half ate a controlled diet before measurements were taken while half fasted for 8 hours. No major differences were noted in signs/symptoms of muscle damage, but researchers said fasting may “generally affect common indirect markers of muscle damage”.

27. Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. (2005) https://www.ncbi.nlm.nih.gov/pubmed/15741046

This article reviews the benefits of IF and calorie restriction: extended lifespan, increased resistance to age-related diseases, improved health in overweight people, reduced risk factors for stroke and heart disease, and increased insulin sensitivity. They review some of the mechanisms of how this works and state that they may be similar to the way exercise works to improve health. These mechanisms are: reduced oxidative damage and increased cellular stress resistance. It does not prefer one diet method over the other.

28. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. (2007) https://www.ncbi.nlm.nih.gov/pubmed/17306982

This is a mouse study that found that both calorie restriction and IF diets can protect against age-related deficits in cognitive function.

What We Know and Don’t Know

Taken together, the majority of the evidence shows that any form of calorie restriction will improve health and longevity. Intermittent fasting does not appear to be superior to traditional calorie restriction, but it is a safe and healthy option for most people. It turns out fat loss and insulin sensitivity can be increased with or without fasting, as long as calories are reduced. Additionally, the research does not support the notion that your metabolism will be protected by choosing IF over calorie restriction. Both diets seem to slow metabolism. Both diets also seem to upregulate autophagy, even without fasting. Many of the research studies with the most exciting conclusions associated with IF were done on mice. Their findings overall do apply to humans, but to a lesser extent. This is common with rodent research since humans are more complex and more difficult to control.

I was unable to answer several of my research questions. I still don’t know when the body switches from burning glucose to burning fat or whether both are being burned all the time at different rates. The research shows that people do burn fat without having to fast for 12-48 hours to completely deplete their glycogen stores. Otherwise, how would people who are not fasting ever be able to lose fat? I didn’t find much information regarding an upregulation of human growth hormone on either diet. I also wasn’t able to find much on ghrelin, the hunger hormone. Studies varied on whether people were able to tolerate traditional diets or IF more easily in regards to feeling hungry.

Conclusions and Applications

The main take-away here is that a reduced calorie diet has a lot of health benefits. These include: resistance to heart disease, diabetes, obesity, cancer, Alzheimer’s disease, and other effects of aging. Intermittent fasting does not seem to have any unique benefits. However, it may help some people reduce calories. It’s important to keep in mind that these results were not only seen in overweight people and animals. Even people of healthy weights were protected by reduced calorie diets that were below what was needed to maintain their weight. This evidence suggests that all healthy weight and overweight people would benefit from reducing calorie intake even though their metabolisms will likely slow due to adaptation.

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