Complex biological systems (you!) have an incredible ability to adapt to their environment. For example, if we challenge ourselves while enjoying our favourite form of exercise or go a day without eating, biology will change in response. Not only do they adjust to respond to the present challenges, but biological systems also adapt to that experience to better deal with it in the future. It is interest in these adaptations that is leading to a rapid increase in research into fasting and understanding its effects on health, ageing and disease.
What the different types of fasting and why is it important to categorise them?
There are many different types of fasting and it is important to distinguish between them as they have different physiological outcomes, caused by different molecular mechanisms, each resulting in different adaptions by our bodies.
Time-Restricted Feeding (TRF) – Enjoying your food within a defined eating window of 4-12 hours each day. For most people, a 10-12 hour window fits into their lifestyle best!
Intermittent Fasting (IF) – Fasting for 24 hour periods with a regular frequency. There are two common forms:
- 5:2 diet: Out of the 7 day week, on 5 days you consume as much as desired and on 2 days each week you cut your energy intake to between 0-700 calories (the 2 fasting days are usually not done consecutively)
- Alternate Day Fasting (ADF): Alternating days of fasting and eating as much as desired
(Multi-Day) Prolonged fasting (PF) – these are usually longer fasts that can take many forms. A common example of a prolonged fast would be a water-only fast for 48 hours which you repeat once a month. When distinguishing between the different forms of prolonged fasting, there are three important variables to considering: the energy intake each day, the duration of the fast and the frequency with which the fast is repeated.
Fasting Mimicking Diet (FMD) – A clinical intervention developed by Valter Longo developed to help investigate the positive and potentially negative effects of fasting while minimising safety and compliance concerns. The human FMD consists of a 5-day regime providing between 725 and 1090 kcal each day, with a macronutrient content selected to mimic water-only fasting but a micronutrient content aimed at maximising nourishment.1
| Fasting regime | Duration of Fast | Frequency of Fast |
| Time-Restricted Feeding | 12-20 hours | Every day |
| IF – 5:2 | 24-36 hours | 1 to 2 days per week |
| IF – ADF | 24-36 hours | Every other day |
| Prolonged Fasting | 48-120 hours | Varies – anything from once a week to a few times a year |
| Fasting Mimicking Diet | 3-5 days | One to a few times a year |
How do complex biological systems respond to nutritional challenge?
Nutritional challenge causes dramatic changes in cellular signalling, which leads to changes in gene expression, metabolism, mitochondrial function and circadian rhythms. These changes occur as part of an intentional, adaptive and coordinated response, which give the biological system an improved ability to deal with the present nutritional challenges as well as future ones.
Benefits of TRF
The growing body of evidence showing the positive health benefits of enjoying your food within a defined eating window is quite remarkable considering the ease with which you can implement this lifestyle change.
One key positive impact is on your circadian rhythm. Circadian rhythms are daily 24-hour cycles in metabolism, physiology and behaviour that can be sustained even under constant light or dark conditions. Chronic disruption to the circadian rhythm causes metabolic diseases and contributes to the ageing process.1
So how can you help keep your circadian rhythm in sync? Your feeding/fasting cycle profoundly affects your circadian rhythm system on both a cellular and organism level. Food intake causes a cascade of changes in gene expression leading to anabolic metabolism (the building up of molecules). This change in metabolism will tell a cell’s circadian clock that it is food time, inhibiting the signals that stimulate sleep and repair pathways.
How does this impact other components of your health?
TRF is linked with lower blood cholesterol, lower body fat, lower excess inflammation, improved cardiac function and improved sleep! TRF also increases brown adipose tissue production (which increases metabolic rate), increases fatty acid β-oxidation and reduces liver glucose production.1
One of the most exciting studies2 on TRF compared mice fed a high saturated fat diet (HFD) within 8-12 hours and mice fed the same diet with constant access to the food. The HFD is usually used by scientists as a mouse model to study obesity. However, this study found that just feeding the mice the same high saturated fat diet within 8-12 hours, helped prevent and reverse metabolic diseases that are associated with eating the high-fat diet with constant access to food.2
Benefits of Multi-Day Prolonged Fasting
The absence of food for more than 24 hours causes further significant changes in metabolism that are regulated through the specific nutrient-sensing systems of biological systems. For those of you that are interested in the biochemistry underpinning those changes, below, is a more complex examination of some of these nutrient sensors and the switches and levers that they flick in response to food scarcity.
Mammalian Target Of Rapamycin (mTOR) – mTOR is a protein sensor. During a fast, the lack of protein downregulates mTOR, which signals cells to start a recycling process called autophagy. This clean-up process not only reduces energy expenditure in response to the current fast but help removes dysfunctional cellular components that make the cells more energy efficient.
AMPK – AMPK is a protein that responds to low cellular energy status. One signal of low energy that AMPK responds to is the concentrations of ATP and AMP. ATP is the universal energy currency molecule used by cells as an energy source for many cellular reactions. When ATP is used, it is converted to AMP or ADP (which in turn can be converted to AMP). As a cell uses up its ATP, the AMP concentration rises signalling low energy, which stimulates AMPK to kick into action. AMPK starts flicking levers and switches that signal cells to start breaking down fats, break down dysfunctional mitochondria and build new mitochondria. As before, by breaking down dysfunctional mitochondria and building new ones, this allows the cell to improve its energy production in the future.
Insulin – Insulin is a hormone that is secreted in response to high blood glucose. During a prolonged fast of more than 24 hours, humans are likely to have depleted their glycogen stores resulting in a fall in blood glucose concentrations. This leads to a drop in insulin which signals to cells to switch to using fats as a fuel.
More research is needed into how soon into a fast each of these nutrient sensors start to flick their levers and so what is the minimum length of fast needed to achieve the benefits that they provide.
Would challenging yourself by fasting be positive for you?
There is a growing body of research showing the benefits of all types of fasting on human health and for the treatment of disease. Indeed, some clinicians are using fasting as a clinical intervention for the treatment of metabolic disorders such as type 2 diabetes and obesity.
However, fasting may not be suitable for pregnant or breastfeeding women and is not for those with a history of eating disorders. If you would like some help with your relationship with food, then have a read of some of the really helpful advice from BEAT.
If fasting is a completely new idea to you, then try enjoying your food within a 10-12 hour window and see how you feel. If this is something that you feel comfortable with, then maybe try a longer 24 hour fast.
If you want to try fasting for longer than 24 hours, it is advisable to let your doctor know, drink plenty of water and listen to your body. If you have to stop a fast because you don’t feel great, that is absolutely fine! You can always give it another go another time!
References
1) Longo, V. D., & Panda, S. (2016). Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab., 27304506. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27304506
2) Chaix, A., Zarrinpar, A., Miu, P., & Panda, S. (2014). Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges. Cell Metab., 20(6), 991–1005. doi: 10.1016/j.cmet.2014.11.001