For National Fasting February in 2019, a group of LifeOmic employees voluntarily spent 90 to 120 hours in a fasted state “for science”. For more than a year we had been researching and reading scientific literature reviews on the mechanisms of prolonged fasting and its potential benefits for aging and longevity. But we wanted to experience a prolonged fast ourselves, measure its outcomes, and be able to better relate to our LIFE Fasting Tracker users. More recently, our CEO Dr. Don Brown, embarked on a 5-day modified fast. We describe what we experienced below.
For our company 120-hour fast, we used the Prolon “fasting-mimicking” diet developed by Dr. Valter Longo at the University of Southern California. Prolon is a plant-based low calorie, low protein and low carbohydrate diet that puts the body in a similar metabolic state as does water fasting. It mimics fasting by restricting calories (< 800 calories per day), elevating ketone levels in the blood and lowering levels of glucose, insulin, insulin-like growth factor 1 (IGF-1) and IGF-binding protein. The Prolon fasting-mimicking diet has been used in dozens of human research studies and clinical trials, including some recruiting and active trials. The diet is being investigated for potential benefits in patients undergoing chemotherapy and in other cancer patients.
Our CEO created his own “fasting-mimicking diet”. He put a couple of cups of mixed greens in a bowl and sprinkled on a tablespoon of olive oil, some salt, and a dozen almonds. This single, 250-calorie “meal” was all he ate everyday for 5 days.
The Prolon diet and Don’s version of a fasting-mimicking diet allow you to garner the impacts of a prolonged fast without potentially problematic side effects such as electrolyte imbalance or gut upset from a complete lack of dietary fiber. More on that below.
So let’s get to what we experienced on our multi-day fast! What can you expect if you embark on a prolonged multi-day fast, whether a water fast or a limited calorie fast? Below we detail some of the experiences, physiological and metabolic changes you can expect, based on our own experience and the underlying mechanisms of fasting!
Plan for Fasting “Crutch” Calories
Very few intermittent or prolonged fasting protocols used in human studies and clinical trials call for absolutely no calories or nothing except for water. In most studies of alternate day fasting (24-36 hours) and other multi-day fasting schedules, researchers have used dietary interventions that call for around 500 calories per day on fasting days.
Thus, when practicing a multi-day fast you can plan to take in some limited amount of calories, especially if this is your first fast beyond 18 to 24 hours. Don’t worry about a few calories here and there breaking your fast and removing its benefits. Eating small amounts of the right kind of food can help you get through a longer fast and won’t hurt your results. This is how the Prolon fasting-mimicking diet works. It keeps you in ketosis while taking the edge off of your hunger and low blood sugar.
What can you eat and drink that will keep you in a fasted state or a metabolic state of ketosis? Focus on low carbohydrate and low protein foods that contain high dietary fiber, unsweetened teas and coffee, along with water with electrolytes. For example, you might enjoy a 100-calorie packet of almonds, some green matcha tea, a few raw vegetable slices dipped in olive oil, kale chips, raw coconut shreds, etc. You can also consume these calories in an OMAD (one meal a day) or time-restricted eating schedule (e.g. a 16:8, or eating 9am to 5pm), so that you are spending most of every 24 hours in a true fasted state.
Fasting Tip: Wait until after your daily workout or bout of physical activity to eat your fasting day calories, because you’ll likely be most hungry anyway at that time. If you eat before, you’ll be tempted to eat more afterwards and go over your fasting day calorie goal.
Family May Express Concerns; Ask for Social Support!
It’s much easier to fast with family and friends, especially on a prolonged fast. Some of our LifeOmic employees asked their spouses to fast with them for the week, and all of us chatted online throughout the week to share our experiences and lend support. This helped tremendously, and is one of the biggest reasons that some of us decided to push through times when we wanted to break our fasts before the 120 hours was up.
It can be difficult to go on a multi-day fast if you don’t have family support or if family expresses concerns. We asked other LIFE Fasting Tracker users to share how they deal with critical comments or concerns about their fasting – check out some of the responses here. If you encounter concern from your family and friends, try sharing your health motivations to fast, talk to them about the research you’ve done to prepare for your fast and accentuate how you are carefully considering your safety (e.g. you’ve talked to a physician, you’ve calculated and planned out your electrolyte requirements, you’ll be monitoring your blood glucose and ketone levels, etc.) You can also link family and friends to our fasting FAQ here.
Whether you are practicing regular intermittent fasting or planning to soon embark on a multi-day fast, consider creating a new Circle in the LIFE Fasting Tracker app to invite others to join you, or browse for a Circle to join others on a fast.
If you are wondering if you’ll be hungry during a prolonged fast, the answer is yes. Unfortunately, even regular intermittent or alternate day fasting won’t lower your hunger hormone levels over time – you’ll regularly feel hungry on fasting days. These hunger sensations may also be heightened for women, who have been reported to have higher fasting levels of ghrelin, the hunger hormone.
However, how you experience hunger may be different than you expect. You might find that you begin to have a different mental relationship with your hunger over time, recognizing it for the rise and fall of hunger hormones that it is. You might even begin to be able to observe your hunger and food cravings as you might observe your wandering thoughts as you try to practice mindful meditation, from a place of non-judgement, transcendence and non-reaction. You’ll be hungry, but you may not react to it as much as you think. You may even begin to appreciate it as a signal for your body to hunker down and become more stress resistant.
When and to what extent you experience hunger while fasting depends somewhat on whether you are naturally an early breakfast person, or whether you are accustomed to going to bed on a full stomach. But hunger also follows a daily rhythm known as a circadian rhythm. Your hunger hormone ghrelin is largely responsible for the coming and going of those stomach groans we call hunger. Ghrelin is produced primarily by the stomach and increases appetite and food intake. Ghrelin levels typically observe a circadian rhythm, cycling up and back down every day. Ghrelin levels rise throughout the day, hitting a peak in early to late afternoon, and slowly wane as you prepare for sleep.
However, ghrelin levels also slowly decrease on average over a multi-day fast. This is why, if you fast for 2-5 days, you’ll probably find that the first few days are the most difficult while your hunger sensations decrease slightly after that, even if you have daily peaks in the early afternoon – especially after a bout of exercise!
“Ghrelin is a peptide secreted in the gut that is reduced on feeding and has been implicated in the regulation of feeding behavior and energy balance. Obese subjects have lower fasting ghrelin concentrations than do lean subjects but have impaired suppression of plasma ghrelin in response to a meal.” – Heilbronn et al., 2005
So while you will be hungry while fasting, you can take comfort that it’ll probably get easier with time, at least during a multi-day fast. Also, if you make sure that you have something fun or productive to do during your ghrelin peaks throughout the day, you might find that your hunger has waned by the time you have the chance to think about food again! Ghrelin levels are also low when you first wake up. So if you can push past the hunger when going to bed on fasting days, you’ll likely wake up feeling much more prepared and energized to just drink your coffee and carry on with your fasting.
Fasting tip: Keep a busy schedule, particularly on the first few days of a prolonged fast, and keep plenty of flavorful drinks (flavored water, tea, coffee, etc.) around when food cravings strike. If you get really hungry, try a few minutes of mindful breathing to bring your focus to your breath or non-judgmentally observe your hunger sensations without acting on them.
You might find that even when you aren’t actively feeling hungry, just the sight of food during your prolonged fast can make you salivate and feel “starving”. So it’s best to stay away from scrumptious foods while on a prolonged fast, or empty your refrigerator of everything except for your low protein and low carbohydrate fasting “crutch” calories before you start, so that you aren’t tempted. (Although sometimes this can be comforting, like when I walked into a cafe-bakery while on the Prolon fast and just stood there smelling the goodness for several minutes… It helped just to order something, some berry herbal tea!)
From our nutrition FAQ:
A motivational “wanting” to eat, i.e., food craving, can be triggered by external cues, hunger states or simply imagining the sight, smell and taste of palatable foods. Food cues in the surrounding environment activate the brain reward system. This reward system preferentially engages our attention towards calorie dense foods. This happens especially when we are hungry, increasing our motivation to eat (i.e. food craving). More specifically, if we pay attention to food cues surrounding us in our daily life (e.g., the appetitive smell of a freshly baked chocolate cake or if we see golden crispy french fries or a delicious melted cheese pizza), the brain is triggered to search for calorie dense foods. And this triggering is augmented when we are hungry.
Fasting Tip: Avoid environments that encourage you to eat unhealthy and that have the potential to induce food cravings and overconsumption, particularly if you are fasting and determined to reach your goal. Whenever you do experience food cravings, “try not to immediately give in to the urge to consume the food, but rather focus on and accept the bodily sensations and thoughts that accompany this urge,” a mindfulness-based technique used by Alberts et. al (2010). By using this exercise, “the primary aim of this approach is not to limit food intake, but to increase awareness of the automatic pattern that usually emerges in case of food cravings,” Alberts et. al (2010) explains.
You can use this mindfulness approach on a prolonged fast in order to avoid eating too many fast-day calories or eating them all (~500 calories) too early in the day. Also try to eat slowly to savor the calories that you do get while fasting.
“The [Prolon] muesli bar was quite delicious. It tasted like a normal healthy muesli bar, just a bit more oily [coconut oils!]. It had been a long time since I was so mindful about eating something. I spent about 3 minutes enjoying that single 43-gram [200 calorie] bar.” – Zhenya, LifeOmic
Rising Ketone Levels
As you progress beyond 16 hours of fasting, if you measure your blood or breath ketone levels (for example with the Keto-Mojo blood ketone meter or BIOSENSE) you’ll notice that these start to slowly rise above baseline. Your ketone levels will also jump up each progressive morning of a multi-day fast. Rising ketone levels are a signal that your body is burning fat for fuel and using fatty acids to produce ketones in your liver.
Ketones serve as a highly efficient alternative energy source for your brain and other organs. But they also have a range of other benefits when present in high numbers in your bloodstream. Groundbreaking research has revealed that ketones serve as signaling molecules, like hormones, that can initiate cellular processes and even change gene expression to make you more resilient to stress. For example, ketones may activate genes that help in fat metabolism and also protect your DNA from damage. A cycling ketogenic diet, or a regular cycle of high ketone levels, has been found to improve healthy lifespan and memory in aging mice, based on research by John Newman at the Buck Institute for Research on Aging. Research also suggests that ketone molecules including beta-hydroxybutyrate protect the cardiovascular system from the impacts of cellular senescence that occurs with aging.
Alertness and Energy Boosts
People often report during prolonged fasts that they begin to feel particularly alert, especially after 18 to 24 hours. This may be in part due to rising cortisol levels with prolonged fasting.
There is data suggesting that your cortisol or stress levels will cycle daily but rise throughout a prolonged fast. Cortisol levels reach low points when your ghrelin or hunger hormones are highest and high points in the evenings when ghrelin levels are lowest. Cortisol levels also slowly rise over the course of a multi-day fast as your hunger slowly dampens. This is your body telling you to (in an evolutionary sense) hunt for food, just as cortisol tells birds caught in a sudden spring snowstorm to stop singing, suspend reproduction, relocate and making finding food a priority.
In other words, cortisol can be a great thing in healthy doses. It can increase energy levels, alertness and the activity of brain cells – as long as it doesn’t become chronic. The key is how long it stays elevated, and when. In one study of healthy young women, “increases in cortisol were significantly associated with a subsequent rise in activeness, alertness, and relaxation, and a trend-level reduction in stress and nervousness.” It helps to consider that exercise also temporarily raises your cortisol levels in ways that prompt your body to adapt by ramping up stress reduction and anti-inflammatory processes.
“[I]n response to transient elevations in cortisol during daytime exercise, there is a substantial and persistent nocturnal suppression in the hormone levels.” – Hackney & Walz, 2013
Intermittent fasting may do something similar, transiently increasing cortisol levels but in the process triggering the body to initiate adaptive responses that lower stress hormone levels long term.
“Similar to exercise, fasting for time periods sufficient to flip the metabolic switch results in the activation of AMPK in muscle cells which, in turn, can activate SIRT1. Consequently, gene expression programs and posttranslational modifications of extant proteins that promote mitochondrial biogenesis [more mitochondria], autophagy [cellular recycling], and cellular stress resistance are activated, whereas mTOR and overall protein synthesis are suppressed.” – Anton et al., 2018
A Need for Electrolytes
It’s important to stay hydrated on a prolonged fast. For one, drinking water and unsweetened teas will keep you feeling more satiated while you are in a calorie deficit. However, it’s very important, especially as you will likely increase your fluid intake while fasting, that you also consume electrolytes such as sodium, magnesium and potassium in order to avoid overhydration and electrolyte imbalances. Insulin also affects renal sodium handling, such that your body sheds sodium when your insulin levels drop as they will on a prolonged fast. This helps explain why high insulin levels are associated with hypertension and why blood pressure lowers during intermittent fasting. (Talk to your doctor if you are hypertensive and on a low-salt diet and practicing prolonged fasting, to determine how you should modify your salt intake while fasting.)
You can address your electrolyte needs while fasting by drinking teas with some pink salt added and taking potassium and magnesium supplements – a daily multivitamin may also work if it contains these electrolytes. Also look for packets of electrolytes designed for hikers and runners for example, and water that contain electrolytes (e.g. SmartWater).
Guidelines for recommended electrolyte consumption for adults over the age of 18:
- Sodium: 5,000 mg of salt per day, or 1,500–2000 mg of sodium.
- Magnesium: 300 to 500 mg per day
- Potassium: 1000 to 3,500 mg per day
*Sodium needs may be a bit higher for individuals on a keto diet or prolonged fast, when low insulin levels cause sodium to be flushed from the system. You may want to increase your sodium intake to closer to 5000 mg per day. Speak to your physician about this if you have hypertension.
You may experience some fatigue and feelings of weakness, lightheadedness, slowness or lack of motivation throughout a prolonged fast, especially in the first few days. Fatigue in particular is normal as your body adapts to this period of low calorie intake. Fatigue may occur as your body is transitioning from burning readily available sugars to mobilizing and burning fats; you may even go through “carbohydrate withdrawal” in a sense.
These symptoms can be signs of low blood sugar or hypoglycemia, a condition that can affect you while fasting particularly if you are accustomed to frequently consuming added sugars, have insulin resistance or liver issues such as fatty liver. While you can improve insulin resistance and hypoglycemia over time by practicing intermittent fasting, you may need to consult your physician and ease into prolonged fasting if you do experience a range of hypoglycemia symptoms while fasting.
In the absence of diabetes, a condition for which you will need to work with your physician, you can work on your blood sugar regulation to prevent hypoglycemia during prolonged fasts by engaging in regular physical activity, increasing your intake of dietary fibers and vegetables, reducing your intake of added sugars and simple carbohydrates, and easing your way into fasting by reducing snacking in between meals and practicing overnight fasting for 12 or more hours. A healthy liver and insulin sensitivity are important components of being able to regulate your blood sugar levels during a prolonged fast.
If you are only experiencing slight fatigue and side effects of low blood sugar while fasting, you might find that drinking a cup of coffee in the morning helps you to feel much better. We definitely did throughout our Prolon fast at LifeOmic! Coffee not only contains caffeine that can help counteract fatigue, but regular coffee consumption appears to be related to improved insulin sensitivity. Plant compounds in coffee, including polyphenols and chlorogenic acids, act to reduce inflammation and improve insulin sensitivity by activating AMPK. (However, if you already have impaired blood sugar control for any reason, caffeine can acutely make this worse. Also in an update from the Prolon team, you may want to avoid more than one cup of coffee per day on a fast as caffeine may activate PKA, a protein that is reduced by prolonged fasting.)
You might find that you sleep really well while practicing prolonged fasting (although the opposite can be true if you experience symptoms of low blood sugar). Healthy amounts of sleep will help give you energy and better regulate your blood sugar while on a prolonged fast. Therefore, be mindful of behaviors that could disturb your sleep while you are fasting, such as consuming caffeinated teas at night.
Starting 18 to 24 hours into an extended fast, you may experience feeling cold, especially in your extremities. You might even find yourself layering on sweatshirts or needing a space heater in your office space.
Studies in animal models have revealed that intermittent fasting can reduce blood pressure, heart rate and body temperature. This is likely because intermittent fasting activates the parasympathetic nervous system or the “rest and digest” functions of the autonomic nervous system. Human studies have shown that fasting can improve cardiovascular function and resilience through reduced blood pressure and post-exercise heart rate. So while feeling cold doesn’t seem like a positive response to fasting, it may actually be a sign that your body is going through a normal adaptation to intermittent fasting and fat burning in a way that will protect you from cellular stress and tissue damage over time!
Feeling cold and sweaty can also be a symptom of low blood sugar or hypoglycemia, so it’s important to monitor yourself for other symptoms and talk to your physician if your symptoms persist or worsen.
Euphoria, Mindfulness and Mental Clarity
You might find, particularly in the later half of a 5-day or other prolonged fast, that you experience moments that are often described as euphoria, a sense of being present or mindful, and mental clarity. Time may even feel like it’s going slower, as one of our employees and Prolon fast participants put it.
“I felt like time was flowing in a more constant manner. When not fasting, I get upset about time moving too slow, or I feel like it moves too fast when I enjoy something. I wondered if there was such a thing as ‘hunger high’. I felt like my mind was behaving differently than normal, and it was an interesting experience. […] The main take away from the 5-day fast for me was that it helped me get rid of stress and anxiety. I felt like my mood fluctuated less than usual throughout the day.” – Zhenya, LifeOmic
Mental clarity and improved cognitive function have been associated with ketogenic diets or the metabolic state of ketosis brought on by fasting. Nutritional ketosis is often used as a treatment for people with epilepsy or other seizure-related disorders, because ketone bodies are an energy source for the brain that don’t produce as many reactive oxygen species and inflammatory chemicals through the process of their metabolism as glucose does. Relying on ketones for energy also prompts brain cells to become more efficient, for example by producing more mitochondria inside of neurons and thus improving how much “clean” energy they can produce.
The improved cognition, “euphoria”, lowered anxiety and mood-boosting impacts of intermittent fasting may be related to ketones as well as to a brain-protecting chemical called brain-derived neurotrophic factor or BDNF. Ketones have recently been found to change gene expression in ways that may produce more BDNF in the brain. BDNF in turn has anti-inflammatory and antidepressant effects and can promote growth of new connections between neurons. The effect of intermittent fasting on BDNF production is being studied by researchers including Dr. Mark Mattson at the NIH.
“It is well known that BDNF plays fundamental roles in learning and memory and also mediates the anxiolytic [anti-anxiety] and antidepressant effects of exercise and antidepressant drugs. BDNF signaling may play important roles in the enhancement of synaptic plasticity by [intermittent fasting], as well as in the production of new neurons from stem cells (neurogenesis) in the hippocampus. Recent findings suggest b-OHB [ketones] also has important signaling functions involving activation of transcription factors. In neurons, b-OHB induces the expression of BDNF, which, in turn stimulates mitochondrial biogenesis and the formation of new synapses.” – Anton et al., 2018
Lowered Fasting Glucose and Insulin
You’ll likely find that your fasting blood glucose levels drop* over time throughout a prolonged fast, as do your insulin levels. Lowering your blood glucose and insulin levels is good for a variety of reasons. Chronically high blood glucose and insulin put you at risk for diabetes and heart disease. These molecules also tell your cells that “times are good” and signal them to grow while bypassing cellular recycling and protein cleanup processes that help prevent diseases like cancer and Alzheimer’s disease.
“Reduced fasting insulin has also been associated with increased longevity in humans.” – Heilbronn et al., 2005
Observational studies of prolonged fasting have found that fasting glucose levels typically begin to lower significantly between 24 and 36 hours into a fast, reaching a stable lowered level around 50 hours.
Insulin levels drop to nearly as low as they will reach by the time you are 50+ hours into your prolonged fast, being cut nearly in half as compared to what you started with. But much of this drop happens quickly, even within the first 24 hours. So in case you decide to cut your multi-day fast short, you’ll still have significantly lowered your insulin levels and prompted your body’s cells to begin to pause their “grow and divide” programs and to recycle their components.
“In preclinical studies, cyclic calorie-restricted diets reduce the risk of several cancers and improve the antitumor activity of standard treatments against already established malignancies. In particular, the fasting mimicking diet (FMD), […] repeated cyclically every 3-4 weeks, enhances the antitumor activity of cytotoxic chemotherapy, while contemporarily protecting healthy tissues and stimulating antitumor immunity. Most of these effects are likely mediated by the reduction of blood glycemia and growth factors, such as insulin and insulin-like growth factor 1 (IGF-1). When administered to healthy volunteers, cyclic FMD has been shown to be safe and capable of reducing risk factors for different chronic diseases.” – Fasting-mimicking Diet in Patients Undergoing Active Cancer Treatment, Clinical Trial
*If you do have any blood sugar regulation issues or if you take medications to regulate your blood sugar, you shouldn’t practice prolonged fasting without consulting your physician, as your medication levels will need to change over the course of the fast.
Lowered inflammation, particularly for those individuals with chronic inflammatory issues such as allergies and psoriasis, is one of the boons of intermittent and prolonged fasting. You might find, as I did, that your allergies, from food allergies that cause itchy skin to hay fever to asthma symptoms, improve. Part of the reason for this is that “starving” cells ramp up production of antioxidants and other anti-inflammatory processes.
In a well-fed state, the individual cell in your body is highly acetylated, particularly as you age. This means that various molecules in your cells, including the histone or “packaging” proteins that wrap your DNA up nicely within the core of your cells, are “decorated” with acetyl groups on their lysine (amino acid) residues. Don’t worry if you don’t understand the jargon in that last sentence. What you really need to know is that the well-fed cell has many genes, including those associated with cellular proliferation, turned on. This is because acetylation tends to loosen the packaging proteins that normally keep your DNA wrapped up, and lets your DNA be read for protein production. Your cells may also normally turn off other genes when you aren’t fasting, such as genes related to fat metabolism, stress resistance and damage repair.
That a well-fed cell would turn on cellular proliferation and turn off stress resistance genes makes sense, because why would a cell on a proverbial beach in the Bahamas prepare for winter by stocking up on warm clothes and covering its pipes with insulation? That would be a waste of time and precious cellular resources, while the cell could be growing and reproducing in the sunshine.
But during starvation, things are different. We have a well-preserved starvation “program” that kicks ours cell into a completely different state when food, particularly glucose or sugar, isn’t around. When you fast, levels of a molecule called NAD+ begin to rise because you don’t have the dietary proteins and sugars around that normally convert NAD+ to NADH through the Krebs cycle. NAD+, a molecule whose precursor is Vitamin B3, activates the sirtuins SIRT1 and SIRT3, proteins that remove the acetyl groups we talked about above from histones and other proteins. In this process, the sirtuins silence genes related to cell proliferation and activate proteins involved in creating new mitochondria and cleaning up reactive oxygen species. Ketones on the other hand work as deacetylase inhibitors, turning on other genes related to antioxidant processes and damage repair. All thanks to the body detecting a lack of incoming calories.
“Increase in NAD+ amounts during metabolic stress, as prolonged fasting or caloric restriction (CR), is well documented and tightly connected with sirtuin activation.” – Pirinen et al., 2012
Starvation also prompts the cell to produce a greater number of newer, shiner and more effective mitochondria, the powerhouses of the cell that create energy in the form of ATP, and antioxidants needed to protect them.
The end result to all of this is that prolonged fasting, and likely shorter but regular intermittent fasting, lowers the burden of reactive oxygen species in our cells and lowers inflammation levels.
Weight Loss and Fat Burning
While your resting energy expenditure stays the same during a fast, your body quickly learns to switch to burning fats for this energy. By 18 to 24 hours into a fast, your body begins to rely heavily on fat breakdown for energy. This is a great thing if you have fat you’d like to lose while preserving lean muscle mass.
“After 12 hours of fasting, energy mobilized from adipose [fat] tissue stores was approximately two times that available from glucose production, whereas after 72 hours of fasting the energy released from adipose tissue was sixfold greater than that generated from gluconeogenesis [process by which your liver turns amino acids, for example, into glucose if needed].” – Klein et al., 1993
Our LifeOmic employees lost an average of 5.5 pounds over the course of a 5-day fast, or an average of a little over 3% of their body weight. The percentage of weight loss range was from 1.5% to nearly 7% body weight loss over the course of five days.
Our CEO dropped almost 9 pounds over the course of his five-day modified fast (eating a bowl of mixed greens with olive oil and a handful of almonds, a 250 calorie “meal” once a day).
Fasting Tip: Doing light to moderate resistance activity during your prolonged fast can help to preserve muscle mass while helping your body to burn fats for fuel. Exercise will also further promote ketone production and autophagy, and may help you feel energized through the tougher periods of your fasting. Consider going for walks, rock climbing, swimming, or doing some strengthening or slow flow yoga.
Originally Posted here by Paige Jarreau, PhD