Calorie Restriction and Intermittent Fasting: 2 Approaches for Life Extension

In a nutshell

  1. Calorie restriction and intermittent fasting have been shown to increase lifespan by 1 to 5 years and reduce the risk of age-related diseases, but while calorie restriction can be difficult to sustain, intermittent fasting offers a more manageable alternative.
  2. Time-restricted eating, a form of intermittent fasting, commonly involves daily fasting for 12 to 16 hours and has been shown to provide noticeable health benefits with as little as 12 hours of fasting per day.
  3. Fasting for three days has been found to be the most effective method for maximizing health benefits and extending lifespan.
Photo by Dose Juice on Unsplash.

Maintaining a healthy and balanced diet is key to promoting well-being and reducing the risk of chronic diseases, which in turn can contribute to a longer lifespan. With a wide range of diets available today, individuals can choose one that fits their lifestyle and goals.

However, leading scientists are increasingly pointing out that the timing and quantity of our food intake may be more critical in triggering mechanisms that promote longevity than the specific types of food we consume. In fact, studies have shown that consuming fewer calories without malnourishment can be incredibly beneficial for our overall life expectancy. This can be achieved in two ways: through either calorie restriction or time restriction eating, such as fasting.

What is calorie restriction?

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Calorie restriction involves reducing the number of calories consumed per day by 20-30%. For example, instead of consuming the usual 2000 calories per day, one would only consume 1400 calories per day. This dietary approach yields numerous positive changes in the body’s metabolic functions, resulting in an extended lifespan of 1 to 5 years and significantly improves healthspan.

Interestingly, calorie restriction is currently the only known nutritional intervention that can attenuate aging in humans, as supported by scientific research.1 Flanagan, Emily W et al. “Calorie Restriction and Aging in Humans.” Annual review of nutrition vol. 40 (2020): 105-133. PubMed Source2Redman, Leanne M, and Eric Ravussin. “Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes.” Antioxidants & redox signaling vol. 14,2 (2011): 275-87. PubMed Source Additionally, calorie restriction reduces the risk of various age-related diseases, making it a valuable approach for promoting overall health and wellness.

An example of this eating pattern is a small Japanese island, Okinawa, where the residents have been known to practice mild calorie restriction by reducing their daily intake by an average of 15%. Their diet mainly comprises nutrient-rich fish and green vegetables, providing them with all the necessary nutrients to lead a healthy life. In comparison to mainland Japanese, Okinawans have a higher mean lifespan of 83.8 years (vs. 82.3 years), a higher number of centenarians, and experience reduced mortality from age-related diseases such as cardiovascular disease, cancer, and dementia.3Willcox, Bradley J et al. “Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span.” Annals of the New York Academy of Sciences vol. 1114 (2007): 434-55. PubMed Source It’s fascinating to see how small dietary changes can lead to significant health benefits and a longer, healthier life.

The figure below4Green, Cara L et al. “Molecular mechanisms of dietary restriction promoting health and longevity.” Nature reviews. Molecular cell biology vol. 23,1 (2022): 56-73. PubMed Source demonstrates all metabolic and molecular changes responsible for preventing multiple age-related diseases and the longevity-promotion effect of calorie restriction.


Metabolic changes happening during a caloric restriction diet. Image is taken from Green, Cara L et al. “Molecular mechanisms of dietary restriction promoting health and longevity.” Nature reviews. Molecular cell biology vol. 23,1 (2022): 56-73. PubMed Source

However, there is one small pitfall in this approach: constant calorie restriction is very challenging to sustain long-term, and people find it difficult to continuously eat less and do so for years or even the rest of their lives. Therefore, eating less frequently, i.e., two meals a day instead of three, is much easier for them. That is why time-restricted eating or intermittent fasting has become so popular now.

What is intermittent fasting?

Intermittent fasting (IF) is a dietary approach that involves cycling between periods of fasting and eating. Unlike traditional diets, this approach focuses more on how and when you eat than what you eat.

There is often a blurred line between caloric restriction and IF. In fact, practicing IF regularly can naturally lead to a reduction in overall calorie intake. One of the most common forms of IF is known as time-restricted eating (TRE), where individuals consume all daily calories within a specific window of time, typically 8-12 hours, followed by a fasting period of 12-16 hours. During the feeding window, one can enjoy regular meals and snacks, while during the fasting period, calories are restricted, though non-caloric beverages such as water are still allowed. This approach to eating can be an effective way to manage calorie intake and promote overall health. Let’s explore all types of IF.


Types of intermittent fasting

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There are different regimes of IF depending on the length of fasting/eating windows:

Time-restricted eating (TRE)

It means fasting every day for 12 hours or longer (usually 14-16 hours yield the most benefits) and eating in the remaining hours. In this way, it is easier to skip either breakfast or dinner, adding up these hours to the hours spent in sleep.

One-day fasting

One-day fasting involves going 24 hours without a meal once a week.

Alternate-day fasting

This approach involves fasting or significant calorie restriction (up to 20% of normal consumption) every other day.

Prolonged fasting

It means going a few consecutive days without eating. Most common routines include fasting for two days each week (so-called 5:2 diet), three days every month, or three days every three months.



What is the best way of intermittent fasting?


As you can see, there are different intermittent fasting schedules. But what is the best way of fasting to extend the lifespan and get the most health benefits?

Almost every fasting method benefits health. Fasting offers numerous health benefits by activating natural anti-aging pathways such as sirtuins, mTOR, and AMPK genes, which mimic the effect of mild natural stressors and increase resilience. Fasting has been linked to improvements in blood pressure, BMI, weight circumference, and DNA repair proteins.[/mfn] Mindikoglu, Ayse L et al. “Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome.” Scientific reports vol. 10,1 18341. 27 Oct. 2020. PubMed Source[/mfn]

Even very short periods of fasting, such as TRE, which involves fasting for 12-14-16 hours each day, have considerable health benefits. They improve metabolic health by alleviating large insulin spikes, helping maintain a steady insulin level throughout the day, and improving lipid metabolism.5 Sutton, Elizabeth F et al. “Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.” Cell metabolism vol. 27,6 (2018): 1212-1221.e3. PubMed Source 6Adlouni, A et al. “Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol.” Annals of nutrition & metabolism vol. 41,4 (1997): 242-9. PubMed Source 7 He, Mingqian et al. “Time-restricted eating with or without low-carbohydrate diet reduces visceral fat and improves metabolic syndrome: A randomized trial.” Cell reports. Medicine vol. 3,10 (2022): 100777. PubMed Source It is shown that after five weeks of 16 hours of daily fasting protocol, there was an improvement in blood pressure, oxidative stress, and metabolic health (such as insulin sensitivity). IF also can aid with weight loss8 Stockman, Mary-Catherine et al. “Intermittent Fasting: Is the Wait Worth the Weight?.” Current obesity reports vol. 7,2 (2018): 172-185. PubMed Source Moreover, restricting your eating window to 10 hours per day aligns metabolism with the body’s internal clock.9 Wilkinson, Michael J et al. “Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome.” Cell metabolism vol. 31,1 (2020): 92-104.e5. PubMed Source Timed-restricted eating allows the body to anticipate when to expect food and prepare physiological responses accordingly.

Twenty-four hours of complete food abstinence turns on another powerful mechanism – autophagy. Autophagy is a natural cleansing process aimed at reusing old and damaged cell parts.10 Longo, Valter D, and Rozalyn M Anderson. “Nutrition, longevity and disease: From molecular mechanisms to interventions.” Cell vol. 185,9 (2022): 1455-1470. PubMed Source At this stage, the cells start gradually breaking down and recycling old components while also breaking down misfolded proteins that have been linked to diseases like Alzheimer’s.11 Alirezaei, Mehrdad et al. “Short-term fasting induces profound neuronal autophagy.” Autophagy vol. 6,6 (2010): 702-10.  PubMed Source

After three days of fasting, the body enters proper ketosis, meaning it starts to burn fat for energy instead of glucose and produce ketones. Three days fasting stimulates stem cell regeneration and reboots the immune system12 Cheng, Chia-Wei et al. “Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.” Cell stem cell vol. 14,6 (2014): 810-23. PubMed Source

How does intermittent fasting work?

During the fasting period, the body is deprived of calories, causing it to switch from burning glucose (sugar) to burning stored fat for energy. It happens in the following way: the triglycerides in the fat cells are broken down into free fatty acids, which enter the blood and reach the liver. In the liver, free fatty acids are converted into ketones. The ketones enter the bloodstream and reach all tissues, including the brain. When your body is in ketosis mode, the brain starts using predominantly ketones for its metabolism instead of glucose. Ketosis can develop already after just 12 hours of fasting,13Anton, Stephen D et al. “Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting.” Obesity (Silver Spring, Md.) vol. 26,2 (2018): 254-268. PubMed Source but only by the third day the insulin gets to its lowest point. 14 Klein, S et al. “Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men.” The American journal of physiology vol. 265,5 Pt 1 (1993): E801-6. PubMed Sourcee

Longer fasting, such as five days of significantly reducing calorie intake (up to 250 cal/day) kicks in other physiological responses in the body. It can activate longevity genes, so-called sirtuins. Sirtuins are a class of enzymes that play a vital role in maintaining genome integrity and extending lifespan.15 Lilja, Stephanie et al. “Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans.” International journal of molecular sciences vol. 22,5 2331. 26 Feb. 2021. PubMed Source They are our natural defense systems against diseases and aging.

Important consideration

Remember that restricting your calorie intake and fasting for an extended period of time could be dangerous and unsuitable for some people. Children and adolescents, pregnant or breastfeeding, people with diabetes or people taking certain medications, or with a history of eating disorders shouldn’t practice fasting. Always consult with a doctor or dietitian before beginning intermittent fasting. However, Dr. Satchin Panda, in one of his recent interviews, suggests that a safe starting point for most individuals would be to limit their eating window to 12 hours.



Recap and final thoughts

Time-restricted eating is a popular and user-friendly form of intermittent fasting that can be easily adopted by anyone. It is one of the most natural approaches, allowing your body to anticipate when to expect food and prepare physiological responses accordingly. It is also considered safe for everybody, with 12 hours of daily fasting being a feasible starting point.

If you’re looking to maximize the benefits of time-restricted eating, gradually increasing your fasting window to 14 or 16 hours could potentially yield even more positive effects. Some of the key benefits include improved insulin sensitivity and lower blood pressure, which can profoundly impact your overall health and well-being.

For those looking to activate powerful longevity mechanisms, such as the sirtuins pathway, autophagy, and cell regeneration, longer periods of fasting may be required. While this may not be feasible or safe for everyone, it can be a powerful tool for those seeking to enhance their health and potentially extend their lifespan.



References

  • 1
    Flanagan, Emily W et al. “Calorie Restriction and Aging in Humans.” Annual review of nutrition vol. 40 (2020): 105-133. PubMed Source
  • 2
    Redman, Leanne M, and Eric Ravussin. “Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes.” Antioxidants & redox signaling vol. 14,2 (2011): 275-87. PubMed Source
  • 3
    Willcox, Bradley J et al. “Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span.” Annals of the New York Academy of Sciences vol. 1114 (2007): 434-55. PubMed Source
  • 4
    Green, Cara L et al. “Molecular mechanisms of dietary restriction promoting health and longevity.” Nature reviews. Molecular cell biology vol. 23,1 (2022): 56-73. PubMed Source
  • 5
    Sutton, Elizabeth F et al. “Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.” Cell metabolism vol. 27,6 (2018): 1212-1221.e3. PubMed Source
  • 6
    Adlouni, A et al. “Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol.” Annals of nutrition & metabolism vol. 41,4 (1997): 242-9. PubMed Source
  • 7
    He, Mingqian et al. “Time-restricted eating with or without low-carbohydrate diet reduces visceral fat and improves metabolic syndrome: A randomized trial.” Cell reports. Medicine vol. 3,10 (2022): 100777. PubMed Source
  • 8
    Stockman, Mary-Catherine et al. “Intermittent Fasting: Is the Wait Worth the Weight?.” Current obesity reports vol. 7,2 (2018): 172-185. PubMed Source
  • 9
    Wilkinson, Michael J et al. “Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome.” Cell metabolism vol. 31,1 (2020): 92-104.e5. PubMed Source
  • 10
    Longo, Valter D, and Rozalyn M Anderson. “Nutrition, longevity and disease: From molecular mechanisms to interventions.” Cell vol. 185,9 (2022): 1455-1470. PubMed Source
  • 11
    Alirezaei, Mehrdad et al. “Short-term fasting induces profound neuronal autophagy.” Autophagy vol. 6,6 (2010): 702-10.  PubMed Source
  • 12
    Cheng, Chia-Wei et al. “Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.” Cell stem cell vol. 14,6 (2014): 810-23. PubMed Source
  • 13
    Anton, Stephen D et al. “Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting.” Obesity (Silver Spring, Md.) vol. 26,2 (2018): 254-268. PubMed Source
  • 14
    Klein, S et al. “Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men.” The American journal of physiology vol. 265,5 Pt 1 (1993): E801-6. PubMed Sourcee
  • 15
    Lilja, Stephanie et al. “Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans.” International journal of molecular sciences vol. 22,5 2331. 26 Feb. 2021. PubMed Source
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