The Many Benefits of Intermittent Fasting

Intermittent fasting (IF) refers to regular periods with no or very limited caloric intake. Intermittent fasting may also be called alternate-day fasting, reduced meal frequency, and time-restricted feeding. There are a variety of protocols including: daily fasting for 16-18 hours; a 24-hour fast on alternate days; a fast 2 days per week on non-consecutive days; or calorie restriction for 5-6 days.

Intermittent fasting is one of the latest diet trends in the news; however, fasting is not a new concept. Periods of voluntary abstinence from food have been practiced for centuries by many groups of people around the globe. In ancient Greece, fasting is a part of spirituality practice and has since been adopted as a religious practice by Muslims, Christians, Jews, and Buddhists. One of these fasting ceremonies that continues today is Ramadan. Ramadan is a religious month for Islam, during which Muslims do not eat and drink during the daylight hours. The duration of restricted food and beverage intake is approximately 12 h/day for 1 month. The spiritual and psychological impacts of fasting have been well documented.

The health benefits from fasting were not investigated until the early nineteenth century. In 1915, fasting therapy for weight loss was first recognized by Dr. Otto Folin, a professor of biological chemistry at Harvard University. Over the last century we have learned that fasting is not only a strategy for weight loss, but also for longevity. Recent research has found that regular, short periods of fasting have many benefits including weight loss, better insulin sensitivity, lower disease incidence, reduced inflammation, longer lifespan and improved learning and memory functioning. One theory as to why fasting is so beneficial is that during the fasting period the body’s cells are under a mild stress, similar to exercise, and the cells respond to this stress adaptively by enhancing their ability to cope with stress and to resist disease.

The goal of fasting is to help improve metabolic health, reduce disease incidence, and increase longevity. As mentioned above, recent research has found that regular short periods of fasting have many benefits including weight loss, better insulin sensitivity, lower disease incidence, reduced inflammation, longer lifespan and improved learning and memory functioning. One theory as to why fasting is so beneficial is that during the fasting period the body’s cells are under a mild stress, similar to exercise, and the cells respond to this stress adaptively by enhancing their ability to cope with stress and to resist disease. Another key mechanism is called autophagy.

Autophagy – Pronounced ah-TA-fuh-gee -- is a process that maintains cellular homeostasis and provides substrates for energy generation. Autophagy is induced by food shortage (IF) and inhibited under energy-rich conditions. In other words, your body still stays in balance and can operate in a food shortage, but a handy side effect is that it actually makes energy and cellular regeneration – so you stay younger! This is the longevity piece!

Fasting is not supposed to make you feel overly tired, stressed, or hungry. If it does, it is important to correct for the underlying biochemical or hormonal imbalance prior to fasting. Hypoglycemia is one example of what is not supposed to happen. This may need further investigation and medical supervision as well as a slower reduction in calories and feeding window to reduce side effects.

Fasting is safe for most people. There may be some side effects seen in the first few days such as headaches or lightheadedness, but this typically resolves after 2-3 days. It is also recommend that menstruating women check their hormones including cortisol levels before any significant fasting cycling. Women who are menstruating need to take breaks from fasting regularly to ensure that hormone changes during fasting do not impact normal menstruation. Diabetics may also need medical supervision during fasting to prevent hypoglycemia especially if they are taking medications which may need to be adjusted as blood sugar changes. Those with a history of eating disorders may not be good candidates for fasting. Similarly, fasting is contraindicated for young children and adolescents who have higher caloric needs due to ongoing growth and development.

There are several different ways of fasting. Figuring out what works for you may depend on your lifestyle, work schedule and goals. Often fasting or time restricted eating (TR) is easier to maintain than long term calorie restriction (CR). Here are a few of the more popular fasting protocols:

Intermittent Fasting

·      During an intermittent fasting program, the individual will fast for an interval of time, usually no more than 48hrs, and then eat normally during the other days of the week. The most common example of this is known as the “5:2” diet, where calories are severely restricted for 2 days (preferably non-consecutive), and then normal eating occurs for the other 5 days in the week.

·      Weight loss and fat burning results are seen with this type of intermittent fasting programs.

·      Cellular changes such as autophagy requires fasting program for longer than 48 hours.

Prolonged Fasting

·      The prolonged fasting diet is includes fasting for an extended period. This is usually performed for 4 to 7 consecutive days. The goal is to stress the body over the course of several days to stimulate autophagy. An example of a prolonged fast would be a water fast for 2-5 consecutive days. This is fast is usually done under the supervision of a qualified health professional.

Time Restricted Fasting

·      Time restricted fasting is an eating pattern in which all food intake occurs within a restricted amount of time. This realigns eating patterns with natural circadian rhythms that help control metabolism, physiology, and behavior. Choose between a 6- or 8-hour window, such as 12pm to 6pm, in which all calories are consumed. Your unique Basal Metabolic Rate (BMR), activity level, and weight loss goals will determine how many calories you should eat within the time restricted window.

Alternate Day Fasting (adapted from Dr. Krista Varady’s Alternate Day Fasting)

·      Picking two to four days per week to limit food and drink consumption to no more than 500 calories. Alternating fasting days with normal days of eating. Daily intake includes:

o   2-4 cups of fresh non starchy vegetables

o   3-6 ounces of organic protein such as poultry, fish, seafood, or eggs

o   1 tbsp or ¼ cup from healthy fats such as unrefined olive or coconut oil or from nuts, seeds, avocado, and olives

o   1 medium piece of fruit

o   Water, tea, coffee

Periodic Fast Mimicking (adapted from Dr. Valter Longo’s Longevity Diet)

·      Choose 5-6 consecutive days to complete the fast. This can be repeated once a month, every 3 months or every 6 months. Frequency will depend on weight loss goals. Food and drink consumption is limited to 800 calories per day. Daily intake includes:

o   4 cups of fresh non starchy vegetables

o   3 ounces of organic fish or seafood

o   1 tbsp ghee or unrefined olive or coconut oil

o   ¼ cup nuts, seeds, avocado or olives

o   Water, tea, coffee

ProLon Fasting Program

·      Based off Dr. Valter Longo’s work and recent research, ProLon fasting is a 5-day fasting program done once per month for 3 months. During the 25 days that is non-fasting, it is suggested to eat a healthy diet using ProLon’s Fast Bar for snacks.

·      ProLon meals come in 5 small boxes (one for each day) that include plant-based energy bars, soups, a variety of snacks, drinks, and supplements. A variety of 5 different soup flavors, sesame kale crackers, chocolate dessert bar, olives, and L-drink for energy.

·      “The ProLon Fasting Mimicking Diet is the first and only meal program that has gone through clinical trials at the University of Southern California. Benefits seen in a clinical study of the 5-day ProLon cycle used monthly for three consecutive months”

·      https://prolonfmd.com/

Studies on intermittent fasting find that hunger levels either remain the same or decrease. However, there may be some increased hunger during the adjustment period, but this usually resolves and levels off.

Below is a review of the current research into fasting and it's many benefits.

Longevity and CLOCK gene expression: The molecular circadian CLOCK gene plays a role in metabolic homeostasis. Recent research has found that physiologically feeding behavior, metabolism and circadian clocks are interlinked. The CLOCK gene plays a central role in the regulation of circadian rhythms that affect physiological functions such as metabolism and sleep. Variations in expression in the CLOCK genes mean you will have a greater risk for obesity, and you will most likely experience greater difficulty in losing weight despite following a low-calorie diet and a healthy lifestyle, especially if you stay up late and do not sleep well. 

CLOCK genes are components of the circadian clock comparable to the cogwheels of a mechanical watch. They interact with each other in an intricate manner generating oscillations of gene expression. The underlying principle of circadian clocks is successive gene activation in the form of a cycle: the initial activation of a gene is regulated by the last one in the sequence, making up an auto-regulatory feedback loop for which one cycle takes about 24 h.  

Fasting helps optimize circadian clock expression by increasing enzymatic activity that impacts cellular maintenance, metabolism, lipid storage and insulin secretion. Said more simply, stress from fasting triggers the body to “increase the fitness of the body.”

For those with variations in their CLOCK genes, fasting is indicated for reducing disease risk, maintaining a healthy weight, and increasing longevity.  It is also important to “Go to bed with the sun and rise with the sun” to support optimal circadian rhythm.

Intermittent fasting influences our genetic expression, circadian rhythms, and longevity. It does this is by positively regulating our “clock” genes. Clock genes are present in every cell of our body and are comparable to the cogwheels of a mechanical watch. Through age, illness, and environmental factors such as a poor diet and stress, our clock genes can become misaligned. This causes the genes to misfire, increasing our risk of disease and reducing our lifespan. Research has found that intermittent fasting is a powerful way to reset this process and keep our internal clock ticking longer.

Genetic expression is the process of turning the instructions in our DNA into usable information that programs our bodies to function correctly. A way to understand this is to think about how a computer works. Computers are programmed with code (DNA) and that code tells the computer what to do. Our typing on the computer is the environmental influences - like diet, pollution, stress, illness- that can either support the code or can cause it to malfunction - ie. user error.  This is why we always say our genetics are not our destiny, because we have the power to influence how our bodies work at the most fundamental level. 

Autophagy: Pronounced ah-TA-fuh-gee -- Autophagy is a process that maintains cellular homeostasis and provide substrates for energy generation. Autophagy is induced by food shortage (IF) and inhibited under energy-rich conditions. Recent studies have shown that autophagy is a dynamic process in the biological circadian rhythm, which are controlled by CLOCK genes. Specifically, BMAL1:CLOCK activates the transcription of genes involved in regulating autophagy. Interference with the circadian rhythm of autophagy is associated with many disorders as has been demonstrated in studies of shift work (night work) and its influence on disease rates such as cancer.

Immune function: Autophagy plays an important role in the development, organization, and functions of the immune system, including cell survival, cell defense and regulation of complex immune responses. As an example, autophagy is necessary for keeping T cell production and survival. T cells are essential for fighting off viral and bacterial infections.

Long COVID: Autophagy initiates antiviral activity by directly degrading viral particles (xenophagy) and destroying viral components (virophagy). Secondly, it induces the innate and adaptive immune systems to produce antiviral humoral and/or cell mediators.

Weight Loss: Intermittent fasting (IF) refers to regular periods with no or very limited caloric intake. It commonly consists of a daily fast for 16 hours, a 24-hour fast on alternate days, or a fast 2 days per week on non-consecutive days. Studies have found that IF resulted in weight loss, ranging from 0.8% to 13.0% of baseline body weight. BMI decreased, on average, by 4.3% to a median of 33.2 kg/m2. Waist circumference decreased by 3 cm to 8 cm in studies longer than 4 weeks.

The largest study comparing IF with calorie restriction found that obese adults who followed IF achieved a mean 4.97-kg weight loss over 52 weeks versus a mean weight loss of 6.65 kg with calorie-restricted diets. Furthermore, most of the weight loss with IF is fat loss. One study calculated that 79% of weight loss was owing to loss of fat specifically. The study also found that weight loss doubled (6 kg) when exercise was added to IF and that the practical length of a fast to effect changes in weight appeared to be at least 16 hours.

Diabetes: Fasting improves insulin sensitivity, reduces C-peptide and insulin levels, and decreases hemoglobin A1C level. It is important to note that the use of IF in patients with diabetes poses a risk of hypoglycemia. Diabetics may need medical supervision during fasting to prevent hypoglycemia especially if they are taking medications which may need to be adjusted as blood sugar changes. Current research showed improved glycemic control with lower morning, postprandial, and average mean daily glucose levels in study participants following IF. These improvements regressed once participants returned to their usual diets.

Fat Loss and Heart Disease: During intermittent fasting when glucose reserves are exhausted, fatty acids are released from fat cells in the process of lipolysis. This process is called ketosis. Ketosis increases fat availability in the form of ketones that can be used for energy in the absence of glucose. Fasting also reduces total cholesterol, triglycerides, and low-density cholesterol (LDL) as well as the size of these molecules, lowering the risk of developing heart disease.

Inflammation: Inflammation is an important contributor of cardiovascular disease. Pro-inflammatory factors, such as homocysteine, interleukin 6 (IL6), and C reactive protein (CRP), contribute to the development of atherosclerotic plaque. Intermittent fasting reduces the levels of these pro-inflammatory markers.

Antioxidant Activity: Oxidative stress has an adverse effect on cells and tissues while ANTI-oxidation protects and preserves cellular function. Research has found that antioxidative metabolites are increased during fasting, reducing oxidative stress and modulating lifespan. 

Improved Energy and Mitochondrial Function: Mitochondria are your cell’s powerhouses. They create the energy that your body needs to function properly. Fasting has been found to enhance mitochondrial function and increase energy output.

Several TCA cycle-related compounds (cis-aconitate, malate, 2-oxoglutarate and succinate) and coenzymes (nicotinamide and pantothenate, a precursor for acetyl-CoA) also increased, reflecting enhanced mitochondrial activity in tissues during fasting. This indcates an significant increase in catabolism and anabolism, stimulated by fasting.