Science Behind Intermittent Fasting

ScienceJuly 8, 202215min read

Intermittent fasting (IF)


  • Intermittent fasting is an eating pattern where a person schedules a time for eating and fasting.
  • Intermittent fasting can be classified into three categories: Alternate Day Fasting, Whole Day Fasting, and Time-Restricted Eating.
  • Intermittent fasting is currently one of the most prominent fitness methods practiced when it comes to weight loss and the prevention of obesity.
  • Intermittent fasting can boost brain functions, improve cardiovascular health, reduce oxidative stress, delay aging, and promote long-term survival.
  • Intermittent fasting works by inducing the activation of longevity genes, repair and defense mechanisms.
  • Risks and side effects may be mild, manageable, and temporary. Several cautions must be taken before you start practicing Intermittent fasting.
  • NAD+ is an important factor in intermittent fasting. Taking NMN supplements may mimic the positive effects of intermittent fasting by activating similar pathways and mechanisms for NAD+ increase.


Working on weight management?

When diets no longer work, intermittent fasting may help.

Intermittent fasting attracted thousands of people because of its purported health benefits on overall well-being, aging and longevity, and of course, weight loss.

Especially in the USA, 1 in 3 adults (30.7%) are overweight, more than 2 in 5 adults (42.4%) are obese, and 1 in 11 adults (9.2%) have severe obesity. Data from the National Institute of Diabetes (NIH) and Digestive and Kidney Diseases (NIDDK) show an increasing trend in the obesity rate. 

Therefore, breakthrough strategies to defy obesity and related health complications are needed. And intermittent fasting may be one of them.

So, what is intermittent fasting, is it effective, and how does it work? In this article, we discuss the scientific basis of intermittent fasting and the accumulating research evidence about its beneficial effects on weight, health, and longevity.

Obesity graphs

Increasing obesity trend. Image source

What Is Intermittent Fasting?

Intermittent fasting is a pattern of eating that involves withholding food and/or drink intake for a scheduled or extended period.

It is estimated that people who follow the strict intermittent fasting regimen have an energy intake reduction of 20-40% of the standard daily calorie intake compared to non-fasting regimens. Because of this observation, intermittent fasting is gaining traction as a good approach to losing weight.

Another weight-loss strategy is the ketogenic diet or commonly known as “keto”. In contrast, intermittent fasting is scheduled eating, while keto is a diet type. In keto, the diet is low-carb and high-fat. This puts the body in a metabolic state called “ketosis” where the body becomes very good at fat burning to generate energy.

The most common protocols of intermittent fasting can be classified into three based on fasting hours or schedule: Alternate Day Fasting, Whole Day Fasting, and Time-Restricted eating (TRE).

Intermittent fasting protocols. fast and eatinf days

Image source

Meanwhile, although fasting usually refers to absolute abstinence from food and/or drink intake, some programs developed for intermittent fasting permit low food intake to approximately 25% of the daily caloric needs during the period of fasting.

The science behind intermittent fasting is pretty straightforward. The idea of how intermittent fasting works is based on two principles:

  • Time for eating is restricted. With restricted time, the fewer days or time you eat, the less you eat overall. Hence, there is a calorie restriction from fasting or restricting the time of eating.
  • Metabolic switch from digesting the food just eaten to burning the stored fats. The second one is founded on the principle that during a fasted state, the human body immediately switches from burning available carbohydrates to breaking down the fat reserves automatically.

When there is a limited supply of energy like during fasting or hunger, our body is forced to utilize the fat reserves to be used as the source of energy. Therefore, the body steadily consumes the stored fats and contributes to weight loss and the burning of fats.

What Are The Health Benefits Of Intermittent Fasting?

Intermittent fasting is even more popular among people in the health and fitness community. Contrary to the existing contentious opinions, the benefits of practicing intermittent fasting are not just a fad.

And in reality, the regimen of fasting has been practiced throughout history during the war periods when famine was widespread. Due to the limited supply of food and clean water, people during the old times were forced to practice fasting.

Several health advantages of doing intermittent fasting have been reported in the literature such as improvements in heart function, immune system, glucose tolerance, weight management, fat metabolism, and brain function, and may even help prevent cancer.

Health benefits of intermittent fasting

Health benefits of intermittent fasting

Here are some of the benefits of practicing intermittent fasting and the evidence behind them:

  • Intermittent Fasting Boosts Brain Functions

Research shows that intermittent fasting may keep our brains young and healthy. It has also been shown to improve memory and learning.

Another very interesting study in 2021 found that intermittent fasting can enhance long-term memory consolidation, neurogenesis or production of brain cells, and the expression of a longevity gene called Klotho.

However, it is not clear whether short-term intermittent fasting has positive effects on healthy people. It appears that it has a comparable effect to the regular caloric restriction strategy, but clinical studies have confirmed that intermittent fasting is beneficial in patients with neurological issues including epilepsy, Alzheimer’s disease, and multiple sclerosis. Further animal tests support similar effects in Parkinson’s disease, ischemic stroke, autism spectrum disorder, and mood and anxiety disorders.

Further, mice studies also found that the neurons adapt a high resistance to excitotoxic stress. Excitotoxicity is the process where brain cells become damaged and dead due to the overactivation of excitatory neurotransmitter glutamate receptors in the brain. With alternate day fasting, mice’s brain cell resistance to injury becomes enhanced.

During fasting, the brain heals to become more efficient in all its intended functions. Aside from this, intermittent fasting may increase the levels of brain-derived neurotrophic factor (BDNF), a protein produced in the brain and spinal cord that promotes the survival of our neurons. The reduction of BDNF at old age is one of the factors leading to several brain health problems such as anxiety and depression.

IF and Brain Function

Brain cells adapt to intermittent stressors by enhancing their ability to function and resist disease. Image source

  • Intermittent Fasting Helps in Weight Loss

Perhaps the most common reason for practicing intermittent fasting is its highly-promoted effect as an aid to weight loss. With a shortened window period for eating food, people lose weight due to lesser calorie consumption from food and/or drink. However, it does not necessarily mean one needs to cut the calorie intake to achieve the benefits of intermittent fasting in terms of weight loss.

In general, since intermittent fasting is only strict on the schedule of when you eat, it does not restrict how much you eat. But of course, the unhealthy choice of meals during the eating windows defeats its purpose and may not result in desirable outcomes. During the fasting period, a caloric deficit happens in the body that promotes the weight loss process.

The practice of intermittent fasting gives the body the right hormones responsible for weight loss. The promotion of increased levels of human growth hormone (HGH) and norepinephrine (playing an important role in the body’s fight-or-flight responses) and the reduction of insulin levels are two of the major physiological benefits of intermittent fasting. These factors contribute to the conversion of body fat reserves into available energy.

One study that reviewed 27 clinical trials on intermittent fasting showed that most participants have experienced weight loss, ranging from 0.8% to 13.0% of their baseline body weight. What is interesting is that the occurrence or observation of weight loss happened regardless of the overall calorie intake changes. Most of the participants had a reduction in body mass index by 4.3% on average for a 2 to 12-week study duration.

The use of intermittent fasting as an interventional strategy to aid in weight loss also promises glycemia management or the control of the concentration of blood sugar in the body. Time-restricted feeding may prevent metabolic diseases like obesity even without restricting food calorie intake.

time restricted diet is beneficial for fat loss and weight loss, even without calorie restriction

Time-restricted eating is largely beneficial to combat obesity, even without restricting food calorie intake. Image source

Intermittent fasting also increases a person’s metabolic rate. This means that one person can consume the same amount of food for energy but can burn more calories. Or one person can consume lesser calories and still have increased metabolic rates. The figure below shows that intermittent fasting leads to the browning of fat tissues. Brown fats are more desirable than white fats. Brown fats are a special type of fat tissue that usually gets activated during cold and it helps regulate the body’s temperature.

The best part of brown fats is that they contain more mitochondria, hence they produce more energy, than white fats which is only functioning mainly for fat storage and tissue insulation.

Intermittent fasting and tissue remodeling

Browning of stored fat tissues. Image source

  • Intermittent Fasting Reduces Inflammation and Oxidative Stress and Delays Aging

Oxidative stress is one of the major factors contributing to accelerated aging as well as many chronic diseases such as diabetes, cardiovascular diseases, cancer, Alzheimer’s Disease, and eye degeneration. 

The imbalance of free radicals and antioxidants in the human body induces oxidative stress. This stress is more prominent in the aging population and is correlated with tissue and organ dysfunction.

According to the oxidative stress theory of aging, age-associated organ functional losses are due to the accumulation of different oxidants such as reactive oxygen and nitrogen species (RONS). These oxidants induce molecular and cellular damage to tissues and organs that may contract a disease or disorder over time.

But, how does intermittent fasting play a role in the prevention of aging-driven degenerative processes? Previous research reported that intermittent fasting may help in the reduction of oxidative damage, improvement of cells’ resistance to stress, and increase the cell’s antioxidant capacity.

Intermittent fasting has positive effects on oxidative stress in animal models. Intermittent fasting may result in beneficial adaptive changes that include the activation of AMP-activated protein kinase, mitochondrial network and peroxisome remodeling, and increased production of antioxidant enzymes.

On the other hand, studies on animal models have promising findings about the effect of intermittent fasting to delay the aging process. The evidence included improved aging biomarkers, reduced oxidative stress, and preservation of memory. The combination of calorie restriction and intermittent fasting was even observed to promote longevity and elevated resistance to age-related diseases in rodents and monkeys.

According to Dr. David Sinclair, a renowned geneticist and anti-aging expert from Harvard Medical School, intermittent fasting can promote slower aging. He noted that when a person fasts, he/she turns on the cell’s stress defense mechanisms which include defenses against DNA damage and molecules that cause abnormalities and diseases. One of the pieces of advice David Sinclair shares for slow and healthy aging is “eat less often”.

Other studies detailed how intermittent fasting can lower inflammation in the body. Inflammation is usually one of the body’s healing mechanisms, but chronic inflammation is undoubtedly harmful and promotes chronic diseases and accelerated aging.

A review of studies highlighted that intermittent fasting regimens may lower the pro-inflammatory C-reactive protein (CRP) concentrations in the blood, specifically for overweight and obese individuals with continuous practice. CRP levels in the blood detect the degree of inflammation in the body. Therefore, the lower the CRP levels, the lower the risks of chronic inflammation.

  • Intermittent Fasting Helps to Lessen Cardiometabolic Disease risks

Aside from the reasons stated above on the effect of intermittent fasting on the improvement of inflammation, reduction of oxidative stress, and delayed aging, it also lessens the risks of developing cardiometabolic diseases. This is due to the activation of heart health-promoting metabolic signaling pathways, like the nicotinamide adenine dinucleotide (NAD+) synthesis pathway which is required in a lot of metabolic processes for cell function and survival.

Higher NAD+ levels are positively correlated to overall health and enhanced cardiac functions. During intermittent fasting and exercise, NAD+ levels increase and activate the anti-aging Sirtuin genes. Sirtuins, in their turn, can ameliorate cardiovascular-related diseases.

And of course, since NAD+ levels naturally fall as we age, boosting your NAD+ levels with NMN (Nicotinamide Mononucleotide) supplementation is a direct strategy to support heart health. NAD+ is critical for the body to generate energy in the chemical form of adenosine triphosphate (ATP) and to fuel the high energy demands of the beating heart. Foods that are natural NMN sources include broccoli, cabbage, cucumber, edamame, and avocado.

Therefore, the higher the NAD+ levels in the body, the higher the capacity for preventing different cardiometabolic disorders. To further optimize the positive effects of intermittent fasting, people may consume NMN supplements during the fasting stage to increase NAD+ levels and boost the positive effects.

For chronic heart failure patients who have had myocardial ischemia, intermittent fasting caused significant improvement in fibrosis and long-term survival.

In 2019, a clinical study with 2,001 patients presented at the American Heart Association’s Scientific Sessions in Philadelphia demonstrated that intermittent fasting successfully increased the survival of heart patients and was featured in the TODAY newsletter.

Myocardial infarction and intermittent fasting

Fibrosis is ameliorated in patients with myocardial ischemia that have undergone intermittent fasting. Image source

Who Should Not Practice Intermittent Fasting And Why?

Intermittent fasting is very promising and a lot of people are very interested in starting with it. However, intermittent fasting is not suitable for everyone.

  • Underweight (BMI < 18.5) people should not practice intermittent fasting because further weight loss may not be advantageous. It is also discouraging for those who have an eating disorder.
  • Children under 18 years old are also not advisable to undergo intermittent fasting because they need proper nutrition for growth and development.
  • Pregnant women and lactating mothers are also restricted to practice intermittent fasting because they need proper nourishment for the expected child.

Meanwhile, some people who have health conditions need medical advice before and during intermittent fasting. This includes people taking prescribed medications, patients with Types 1 and 2 diabetes mellitus, people with high uric acid or gout, and those with serious diseases like gastric ulcers or disorders in the kidney, liver, or heart where the effects of intermittent fasting are unknown or may aggravate their conditions.

Risks And Side Effects Of Intermittent Fasting

If done properly, you may reap the maximum benefits of intermittent fasting in optimizing your health. On the other hand, it is also important to be aware of its health risks and side effects to anticipate and/or prevent undesirable outcomes.

Here are some of the risks and side effects of intermittent fasting:

  1. Increased feeling of hunger and risk of overeating

Hunger is the most common side effect of intermittent fasting and is also very challenging. Because food is only allowed during a limited period, the stomach during the fasting period will be empty, feel hungry, and may send signals to your brain to eat. Due to that, with suppressed hunger during the fasting phase, there is a high risk of overeating if you give in to the temptation.

But the hunger urge may just be temporary. A 2020 study enrolled 1,4220 participants to undergo 4-21 days of fasting regimens. The study found that the hunger symptoms are only pronounced during the first few days of the regimens.

  1. A feeling of Tiredness or Fatigue

People who start on intermittent fasting may usually experience tiredness, fatigue, and even feel groggy. Remember that during intermittent fasting, glucose levels are low and energy levels are also low. With an energy deficit, everyone who practices intermittent fasting may feel a bit weak, but for an active person, this might be more bothersome.

Fortunately, this is also not permanent. A clinical trial revealed that intermittent fasting may reduce fatigue as soon as your body adapts to your new eating schedule.

  1. Risk of dehydration

The initial fasting periods may trigger a natural diuresis where the body excretes more water and salt through urination. It is also commonly reported that people who practice intermittent fasting may also forget to drink enough.

Therefore, you are highly encouraged to pay attention to your fluid intake. Monitor how much you drink and check the color of your urine – too dark can indicate that you’re dehydrated.

  1. Headaches and irritability

A meta-analysis of 18 studies also reported that mild or moderate headache is also a common side effect of intermittent fasting.

In another study, researchers have explained that fasting-associated headaches are also associated with low blood sugar levels.

  1. Risk of malnutrition

Some people who have gone too much with intermittent fasting that their body becomes too accustomed to fasting become able to eat only once a day. However, this has a very high risk of malnutrition. If intermittent fasting is unplanned correctly, you might suffer malnutrition which may lead to other health harms. Therefore, it is very important to prioritize healthy eating and consume a balanced diet during the feeding phase.

time-restticted eating or intermittent fasting for weightloss

Image source


Overall, the science about intermittent fasting is mounting. There is a growing body of scientific evidence that support the promising benefits of intermittent fasting by activating the molecules and pathways that enhance health and boost our built-in mechanisms against diseases. If done properly, intermittent fasting is a great strategy for weight loss, health improvement, and life span extension.