Efficacy of IF and Regimen Recommendations

Humans and other animals with circadian rhythms have evolved to have a natural fasting cycle, with fasting during sleep. This fundamental ability to store nutrients and utilize them when not actively consuming food is crucial to life. Inherent to the concept of fasting is that the biochemical processes of metabolism in the body are fundamentally distinct during fasting periods and active nutrient intake periods. This concept has led some to theorize that the biological processes that occur during fasting are important for normal metabolic stability and can be optimized. In particular, as artificial light and stimulants have become pervasive in society, so has their deleterious effects on our circadian rhythm, and potentially our fasting cycles as well.1

Recently, targeted molecular and disease-oriented studies of fasting and caloric restriction have pointed to potential applications for the prevention of some diseases, including cancer, and possible increases in longevity.

IF Regimens and Caloric Restriction

There is still a great deal to be understood about specific fasting regimens: which are most appropriate in the context of prevention and general well-being in healthy adults, and in the case of specific diseases. The general theory is that entering the 'fasted state' confers benefits to health. One potential mechanism of how fasting improves overall health is that as your body depletes the stores of glycogen in the liver ( the long-term storage form of glucose), you begin to metabolize longer-term energy storage sources, such as fats. Intermittent fasting and caloric restriction (no periods of forced fasting, but an overall reduction in calories consumed) are thought to drive the body to more quickly enter the fasted state when energy resources are depleted. The big challenges in this space are: (1) clinical proof of the efficacy of fasting regimens in preventing or treating disease and (2) elucidation of the molecular mechanisms of fasting benefits. However, studies have already demonstrated that fasting has definitely benefits on fasting glucose levels (5.9% reduction), IGF-1 levels (15% reduction; IGF-1 is a factor associated with increased cancer incidence), body weight and body composition (3% reduction in body weight with abdominal fat loss most prominent).2,3,4,5

The entry to the fasted state and the length of it depend on the specific regimen of fasting or caloric restriction. Below we compare intermittent fasting (IF) regimens and speculate about the efficacy of IF regimens based on what we know about ketosis and the circadian rhythm. We compare lean gains (16/8), the warrior diet (20/4), 36-hour fasts, and 60-hour fasts. Finally, we also delve into new data around "fast-mimicking diets" and caloric restriction. The best data out there exists in animal models. Human studies of fasting are lacking at the moment, but there are some conclusions we can draw from current evidence.

Leangains (16:8) and Warrior Diet (20:4)

These diets are meant to narrow the window in which you consume calories. Leangains is 16 hours of water-only fasting, with an 8 hours feeding window, and the warrior diet is 20 hours of fasting with four feeding window. These diets have the benefit of being able to eat everyday while providing caloric restriction, since you can't eat as many calories in one sitting as you could spread out over a day. Physiologically, some individuals will enter a ketotic state with these regimens, depending on your unique biology and your activity level. Typically, liver glycogen stores ( a long-term storage form of glucose that is mobilized during the fasted state) are depleted 12-24 hours after fasting. However, it is logical that maintaining this diet over multiple days will gradually deplete glycogen stores, and promote entry in the fasted state more quickly.

Leangains is the easiest routine to follow to get into fasting if it is completely new to you. A good starter schedule would be to start with lean gains three days a week, and normally eat the other four days, and then week-by-week, increasing lean gains days and reducing normal feeding days until you are on the lean gains schedule 5 days a week. After you are comfortable with this schedule, adding in a day of warrior diet (20:4) per week, until you are on the warrior diet regimen five days a week, and eating normally two days a week. In our experience, we have found that on "normal" eating days, we tend to consume less. Possibly because our metabolisms have gotten used to the lower calorie state, and do not have the machinery ready to metabolize a lot of nutrients.

Your diet during non-fasting days should be balanced, with sufficient proteins, carbohydrates, and fats. Recommended percentages of each macronutrient from the 2010 Dietary Guidelines for Americans:

- Carbohydrates: 45-65% of calories
- Fat: 20-35% of calories
- Protein: 10-35% of calories

Fast Mimicking Diet

There have been several interesting studies that have shown that instead of completely going nutrient-free, a "fast mimicking diet", may be a more sustainable option. In an interesting 2015 paper in Cell Metabolism, it was shown that a fast mimicking diet in mice could enhance longevity, reduce cancer and skin aberrations, increase immune system stem cells, and reduce bone mineral density loss.2Most interestingly, this diet was shown to be effective in middle-aged, and older mice, and resulted in no negative side effects. So potentially, the fast-mimicking diet can confer benefits of fasting, while reducing the incidence side effects of having no calories, even in older, more frail animals.

Just what the perfect fast mimicking diet is, still needs to be explored. A combination of ingredients ranging from 500-1000 calories per day, of nutrient and vitamin rich, low fat, low carbohydrate food is a good place to aim for. Here is our recommendation for fast-mimicking diets:

- 1000 calories: 2 quest bars + 2 cups of almond milk with 1/2 scoop of whey protein powder + daily multivitamin
- 750 calories: 1 quest bars + 2 cups of almond milk with 1/2 scoop of whey protein powder + daily multivitamin
- 500 calories: 1 quest bars + 1 cups of almond milk with 1/4 scoop of whey protein powder + daily multivitamin
- 250 calories: 1 cups of almond milk with 1/4 scoop of whey protein powder + daily multivitamin

36 (6:1) and 60 (5:2) hour fasts per week

These are the most intense regimens, as they require no calories consumed during the 36-hour, and 60-hour fasting windows. Practically, this schedule would mean having your last meal on Sunday night, and not eating until Tuesday morning (36 hours) or Wednesday morning (60 hours). In these fasting regimens, your body is almost certainly in a state of high ketosis, particularly after the first 24 hours of fasting. A good way to work up to these is through the fast-mimicking diet.

For the 36-hour fast, this would entail eating normally six days a week, and then consume a fast-mimicking diet on the 7th day. The gradually, reducing the caloric content of the fat-mimicking diet, week-by-week, until you are consuming water-only on the fasting day. For the 60-hour fast, another leg is added, as we discuss below.

Our recommendations

For those new to fasting the best way to get into the lifestyle is to start slow, and gradually increase your fasting periods/amount of calories consumed. However, everyone's individual needs will vary, and since this is such a new space, there is not a great deal of data as to what regimen will be ideal for you. You may find that five days of lean gains and two days of normal eating is perfect for you, and moving up to the warrior diet doesn't work for you. That's perfectly OK! Below I chart two paths from fasting-naive, to fasting-proficient. One to reach five days of warrior diet per week, and another to reach 60-hour fasts per week. But if certain points work for you, and fasting longer adversely affects your life, then you should stick to that point of balance.

Definitions

- Leangains: One 8 hour window to eat per day
- Warrior diet: One 4 hour window to eat each day
- Fast-mimicking Diet: A high protein, low carbohydrate, high vitamin, controlled calorie diet.
- 36-hour fast: Last meal on Sunday night, next meal on Tuesday morning. Water only during the fast
- 60-hour fast: Last meal on Sunday night, next meal on Wednesday morning. Water only during the fast

Warrior Regimen

- Week 1: 3 sequential days of lean gains, 4 days normal eating
- Week 2: 4 sequential days of lean gains, 3 days of normal eating
- Week 3: 5 sequential days of lean gains, 2 days of normal eating
- Week 4: 3 sequential days of warrior diet, 4 days of normal eating (optional: 2 days of lean gains after warrior diet days, then 2 days of normal eating)
- Week 5: 4 sequential days of warrior diet, 3 days of normal eating (optional: 1 days of lean gains after warrior diet days, then 2 days of normal eating)
- Week 6: 5 sequential days of warrior diet, 2 days of normal eating 

Himalayan Regimen

- Week 1: One 36 hour fast + 1000 calories of fast-mimicking diet
- Week 2: One 36 hour fast + 750 calories of fast-mimicking diet
- Week 3: One 36 hour fast + 500 calories of fas-mimicking diet
- Week 4: One 36 hour fast + 250 calories of fast-mimicking diet
- Week 5: One 36 hour fast
- Week 6: One 60 hour fast + 1000 calories of fast-mimicking diet on the second day
- Week 7: One 60 hour fast + 750 calories of fast-mimicking diet on the second day
- Week 8: One 60 hour fast + 500 calories of fast-mimicking diet on the second day
- Week 9: One 60 hour fast + 250 calories of fast-mimicking diet on the second day
- Week 10: One 60 hour fast

Tips

- Drink LOTS of water during the complete fasts. Food actually contains a great deal of water, and if you don't drink much more than usual you will become dehydrated, which can be dangerous.
- Listen to your body. If there is a certain point, beyond which you cannot function while fasted, or feel long-term effects, stop there. Some fasting and/or caloric restriction is better than nothing. For some, the fast-mimicking diet will be a good stopping point for them. As this regimen may require less willpower to stick with, since you are consuming calories and nutrients on a daily basis. 

At the moment, there are no compelling, large scale studies of human fasting and caloric restriction. These recommendations may change as we learn more.

Additionally, studies suggest that caloric restriction (60% of control diet) negatively affects spatial memory and altered neurogenesis in adolescent rats. This evidence suggests that these dietary restrictions are deleterious for young animals in comparison to the effects on mature animals, so we do not recommend fasting, in any capacity for individuals below the age of 18.6

  1. Longo, V. D., & Panda, S. (2016). Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab, 23(6), 1048-1059. doi:10.1016/j.cmet.2016.06.001

  2. Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., . . . Longo, V. D. (2015). A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab, 22(1), 86-99. doi:10.1016/j.cmet.2015.05.012

  3. Chan, J. M., Stampfer, M. J., Giovannucci, E., Ma, J., & Pollak, M. (2000). Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and prostate cancer risk: epidemiological studies. Growth Horm IGF Res, 10 Suppl A, S32-33.

  4. Giovannucci, E., Pollak, M., Platz, E. A., Willett, W. C., Stampfer, M. J., Majeed, N., . . . Hankinson, S. E. (2000). Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and the risk of colorectal adenoma and cancer in the Nurses' Health Study. Growth Horm IGF Res, 10 Suppl A, S30-31.

  5. Levine, M. E., Suarez, J. A., Brandhorst, S., Balasubramanian, P., Cheng, C. W., Madia, F., . . . Longo, V. D. (2014). Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab, 19(3), 407-417. doi:10.1016/j.cmet.2014.02.006

  6. Cardoso, A., Marrana, F., & Andrade, J. P. (2016). Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning. Neurobiol Learn Mem, 133, 214-224. doi:10.1016/j.nlm.2016.07.013

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