The Fasted and Curious: Purported Benefits and Risks of Intermittent and Prolonged Fasting

During my most recent FaceTime catch up with my mom, she mentioned she was trying out a 5-day “fasting kit”, where she eats a teeny bit of specialized food each day – broth, a couple bars, some teas – to mimic a state of fasting within the body. She said she had been reading up on the benefits of fasting and how it can almost serve as a reset button for your metabolism and immune system, among other things. She even showed interest in these supervised fasting clinics where people stay to undergo prolonged fasts (sometimes upwards of a month!).

As a self-proclaimed food lover and budding scientist, I immediately cautioned her on the physiological risks of extended fasting (read: starvation), but I’m pretty sure I was unable to change her mind at that time. So, mom, this one is for you: I looked into some peer reviewed literature on fasting – most common types of fasting, what happens to your body the longer you fast, and any lasting effects once fasting is broken. To her point, there is a growing body of literature suggesting that short-term fasts could provide a myriad of health benefits. The real question is if extended fasts have any added benefit, or if you’re just hurting yourself by starving your body.

Types of fasting. The most common types of fasting, which are all forms of intermittent fasting (IF), are time-restricted, alternate-day, and 5:2 fasting. In time-restricted fasting, you restrict your calorie intake to a narrower window of time during the day. This might mean that you eat all your foods within an 8-hour window, meaning you’re fasting for the other 16. In alternate-day fasting, you either fast completely or drastically limit your caloric intake every other day. This might mean that you eat 25% of your normal calories on fasting days versus non-fasting days. And in the 5:2 approach, you only do this restriction two days a week; the other five are normal. Beyond these IF approaches are more long-term fasts of up to 40 days (Jesus, anyone?). In all of the aforementioned methods, water is still allowed. There is such a thing as dry fasting, where you even abstain from water during a max 3-day period, but this is significantly less popular due to the severe risks that come with dehydration.

Physiological changes in a “fed” vs. “fasted” body. There is a fundamental metabolic change that happens in your body when you are “fasted” versus when you are “fed”. On a normal diet, a “fed” state means your body has access to carbohydrates or sugars to break down for energy. Our bodies are optimized for this process; we are able to produce more molecules of energy (known chemically as adenosine triphosphate or ATP) from sugars than we can from fats or proteins. However, anywhere between 8-16 hours without food (exact times vary between sources), we deplete these sugars, causing the body to turn to other sources for energy: namely, fat. Fat is broken down to ketone bodies, which undergo further metabolism to give us energy – this is called ketosis. Thus, the main difference between a “fed” versus a “fasted” state lies in the types of molecules our body breaks down to get its energy.

Purported benefits of ketosis. Ketosis marks the switch from metabolizing sugars to metabolizing fats for energy. Since fatty acids and ketones are not our default  metabolic energy source, being in a state of ketosis signifies an acute stress to the body. In theory, this can lead to an adaptive response where our body switches from a growth phase to an energy reservation phase. During this time, several defense and repair pathways can be stimulated, including antioxidant defense, DNA repair, as well as the breakdown and recycling of damaged or old cells in a process called autophagy. The hypothesis is that these pathways, which work to keep us in better overall health, might remain unstimulated if we are constantly in a “fed” state.

In this sense, entering ketosis through fasting can “reset” the body to a more optimal performance. For example, fasting can stimulate autophagy, which in turn can boost immunity in mice, and ketosis can stimulate immune function in cows, presumably through recycling of damaged or old immune cells. Additionally, using fat stores for energy has clear clinical benefits in treating obesity-related and cardiovascular diseases. For example, fasting lowers blood glucose levels and can increase the body’s sensitivity to insulin, which can work to offset type 2 diabetes. And the working idea is that if you regularly subject your body to a mild stress, such as fasting, to elicit an adaptive response, this will carry over into the “fed” state and your body will become more adept at reacting to other stressors and diseases (such as viral infection, potentially?).

Proponents of fasting will also say that being in ketosis can improve cognitive function and physical performance, but human studies investigating those claims are extremely limited. There are some data showing that IF increases endurance, balance, and coordination in animals, but similar studies in humans have yet to be reported. Regarding cognitive function, some preclinical data shows that autophagy can have neuroprotective effects in mice (Alirezaei, 2010; Brandhorst, 2015). Additionally, one clinical trial showed that two years of caloric restriction in healthy adults resulted in a slight improvement in working memory, but sustained calorie restriction doesn’t repetitively trigger a switch in metabolic states like IF does. As of yet, there aren’t any human studies showing that fasting can make you more mentally agile or physically fit.

How long should I fast? Since a growing body of literature suggests that there are tangible benefits to IF, one might naturally wonder if those benefits are proportional to how long the fast is. In other words, if you fast longer, will you benefit more? And the short answer is, well, no. I mentioned earlier that it could take 8-16 hours for your body to switch into ketosis. If you continue to fast, blood ketone levels will rise for about another 1.5 days, indicating that your body is metabolizing an increasing amount of fat for energy. However, around 48 hours into a fast, blood ketone levels tend to plateau. This suggests that ketosis isn’t happening any more significantly 2 days into a fast versus 10 days. Some might argue that staying in a prolonged state of ketosis will allow defense and repair pathways a longer, uninterrupted amount of time to act. But if these pathways are stimulated by a state of ketosis, wouldn’t the same effect be achieved by adhering to a ketogenic diet for a few days? Of course, if the main goal of a fast is to lose weight or to counteract an obesity-related disorder, then prolonged fasting will allow for continued access to fat stores for energy, facilitating weight loss (even though the method of weight loss isn’t sustainable). But if you’re not fasting to actively lose weight, then chances are you won’t experience any additional benefits from an extended fast versus IF.

Risks of fasting. There are risks in anything that we do, and fasting is no exception. For short-term fasts like IF, the risks are pretty mild – aside from feeling straight up cranky, you might have some trouble sleeping, become dehydrated if you don’t allow yourself electrolytes during your fast, and you may experience digestive issues once you break your fast. But the real dangers come with extended fasting. In extended fasting, your blood pressure drops significantly. This can be beneficial in battling high blood pressure, but it also increases the likelihood of fainting and head trauma. Electrolyte deficiency may cause muscle cramping, and you also may feel chronically cold and weak since your body is trying to preserve its energy. Additionally, we have a hormone called leptin that, in addition to regulating appetite, helps regulate white blood cell production (Naylor, 2016; Phillips, 1998);  its levels in the body are directly dependent on the amount of fat we have. Therefore, contrary to the claim that fasting can boost your immune system, you could actually end up weakening it. There’s also a risk of gout – uric acid is another byproduct that is produced during fat metabolism, and if you have too much uric acid in your blood, it can surround joints to cause pain and swelling. And of course, if you exhaust your fat reserves, your body will go past ketosis and start breaking down proteins for its primary source of energy, like muscles and organs. 

Perhaps one of the more unexpected dangers of extended fasting is the refeeding process. Your body adapts to ketosis for energy production after going so long without food, so re-introducing sugars and minerals can actually be quite a shock. At the end of a fast, your body is still in energy preservation mode. When you eat, your body will immediately direct the detected nutrients towards the synthesis of sugars, fats, and proteins – things you deprived your body of during your fast. The switch back to the growth phase requires a lot of auxiliary components, including key minerals like potassium, magnesium, and phosphorus. Since these minerals are likely severely depleted in your cells due to your fast, your body will pull these minerals from your blood, causing a serum electrolyte deficiency. This can impair the function of your blood cells, leading to inadequate oxygen delivery to your body’s organs. Ultimately, this can present as confusion, abnormal heart rhythms, seizures, and even heart attack.

To fast or not to fast. There are few, if any, controlled studies investigating the therapeutic benefits of extended fasting. One thing I noticed during my research for this article is that the the studies I did find either had authors who owned companies selling fasting kits (Brandhorst, 2015), or were conducted at for-profit fasting clinics (Toledo, 2019; Toledo, 2020; Grundler, 2021). It is unclear if the participants in these studies were already paying customers beforehand; regardless, conduction of such studies in a biased environment is a clear conflict of interest. There is more work published on IF, and the consensus seems to be that IF has equal benefit and significantly less risk than extended fasting. So, mom, here’s my take home message: if you fast, do it for like, two days at a time, and then go back to eating that cubed watermelon that I know you have in the fridge. If you really want an extended effect of ketosis, consider a ketogenic diet for a couple days directly after your fast. But please don’t go to a fasting clinic. I personally believe they’re bogus, and they’re *such* a first world problem (paying a lot of money to starve yourself) that I’d feel a degree of second-hand embarrassment if you went.  

Peer Editors: Rachel Cherney and Fanting Kung