Caloric restriction as the name implies is a dietary reduction in energy without necessarily sacrificing essential nutritional requirements. According to Bales and Kraus, caloric restriction is defined as a reduction of average daily caloric intake, between 10% and 40%, without malnutrition and without affecting the intake of essential nutrients like vitamins and minerals. From both definitions, it is necessary to note that adequate or essential nutrition is maintained. This is necessary to rebut the general misconception of the association between caloric restriction and nutritional deficiencies.

Caloric restriction is interestingly the only nutritional intervention proven to potentially abate aging. Evidence from some observational, preclinical, and clinical trials highlights the ability of this method to increase life span by about 1–5 years with an added benefit of improvement in quality of life. It achieves this on a molecular level through cellular and metabolic adaptations which in turn reduces the risk for developing many cardiometabolic diseases. However, with this significant role CR plays, its implementation is often complex and may require unique considerations for elderly people and certain specific populations.

Fasting on the other hand is the reduction in the frequency of food intake without necessarily paying attention to nutritional deficiencies, they usually may or may not take into consideration the caloric intake, especially during non-fasting times. Fasting in recent times has gained solid ground and is widely known and practiced now. There are varied views when it comes to the concept of fasting and its benefits to the body, its upheld by many due to its results especially in weight loss schemes, some health practitioners and nutritionists, on the other hand, advise against it. According to them, it’s a quick fix, and in the long run, it could pose potential health threats.

How do calorie restriction and fasting work?

Research has not been able to adequately explain the connection between calorie restriction and the aging process in humans, in animals however calorie restriction has been found to extend lifespan by affecting processes that are associated with the aging process such as inflammation, DNA modifications, etc.

Fasting on the other hand has been widely researched and based on these findings, it has been observed that during a fast say a 12-24 hour fast, there's a 20% or even greater decrease in serum glucose which causes the body to resort to the use and depletion of hepatic glycogen stores. When this occurs, the body enters into a metabolic state where nonhepatic glucose, free fatty acids, and ketone bodies are utilised as energy sources. Lipolysis is one of the processes the body undergoes to provide non-hepatic energy sources specifically, ketone bodies- Lipolysis then causes an overall reduction of body fat and this translates as weight loss.

Fasting also enhances insulin sensitivity of muscle and liver cells and reduces the production of IGF-1. (IGF-1 also known as somatomedin C is a primary mediator of growth hormone, it has growth-inducing effects on almost all cells in the body by stimulating metabolic effects.)

In combating cancer, fasting has a significant effect, due to the production and use of ketone bodies. Cancer cells are unable to use ketones to produce energy to meet their metabolic demands which induce starvation and cell apoptosis/death.

What are the advantages and disadvantages of calorie restriction & fasting


  1. Fasting aids in weight loss; it induces the production of ketone bodies through the breakdown of fat (lipolysis) this causes an overall reduction of fatty tissue and results in weight loss.
  2. Enhances insulin sensitivity and helps in the management of diabetes; intermittent fasting helps combat diabetes by reducing serum glucose levels, increasing adiponectin levels, and reducing leptin levels in the blood, which improves insulin resistance.
  3. May improve longevity; short-term fasting may reduce oxidative stress and inflammation throughout the body which promotes longevity. It may also contribute to the quality of life by reducing risk factors for the development of cardiovascular diseases.
  4. Reduces the risk of developing cardiovascular ailments; certain clinical studies prove the positive metabolic effects of fasting to the body and how it improves risk by reducing blood pressure, LDL & cholesterol levels, maintaining adequate blood glucose levels, and decreasing pro-inflammatory factors such as C-reactive proteins and cytokines.
  5. May aid in the improvement of neuroplasticity; short-term fasting may improve neuroplasticity and hence reduce the risk of developing certain neurodegenerative diseases such as Alzheimer’s disease.
  6. Helps combat metabolic syndrome and reduce risks accompanied by metabolic syndrome such as hypertension.
  7. Autophagy; fasting may induce autophagy in which is a key homeostatic process whereby the body breaks down unnecessary or damaged cellular components. There have been no conclusive human studies about this, this data is observed in animal studies.


  1. Hypoglycemia; prolonged fasting causes a significant reduction in serum glucose sometimes below the normal which presents with physical symptoms such as dizziness, light-headedness, lethargy it's especially dangerous in patients with type 1 DM and could be potentially life-threatening.
  2. Weight- gain; some people usually, tend to binge eat which increases their caloric intake on non-fasting days in the long run it accumulates and leads to an increase in overall weight.
  3. Risk of developing side-effects and certain nutritional deficiencies; some people on fasting and calorie restriction sometimes develop uncomfortable side effects such as dizziness, low energy, etc. Fasting has the potential to trigger migraines also. There is also the risk of low intake of certain essential nutrients and malnourishment.
  4. It is contraindicated in patients with eating disorders since it can induce them; some people who have eating disorders and are on fasting or calorie restriction are at risk of triggering these disorders, for example, by binge eating and others.
  5. Severe forms of fasting and caloric restriction may sometimes result in excessive weight loss and can potentially result in unhealthy body weight (low body weight) which can affect the person adversely.

What are the different forms of calorie restriction and fasting?

There are many forms of fasting, six are highlighted below with the most popular being the preceding four.

  • 5:2 fasting. This is one of the most popular fasting methods where any amount of calories is consumed for 5 days a week while the caloric intake is restricted to about 500 calories for women and 600 calories for men for the 2 days left within the same week. Usually, it’s required to have one fasting day between non-fasting days.
  • Time-restricted fasting. For this type of fasting, there are eating and fasting windows usually the 16/8 or 14/10 method. The 16/8 method involves a fasting window of 16 hours and an eating window, where the person is allowed to eat within 8 hours in a day. The 14/10 method includes a fasting window of 14 hours and an eating window of 10 hours within a day. Ideally, it is recommended that women fast for 14 hours when this method of fasting is used.
  • Alternate day fasting. Here fasting is done every other day, where there’s a caloric restriction of about 25% or 500 calories, while normal caloric consumption is maintained on non-fasting days. A study found that subjects who utilised this method of fasting for 6 months had elevated levels of LDL which persisted 6months after cessation of the fast.

Eat Stop Eat/24-hour method. In this method, a full 24-hour fast is done. Usually, it’s done once or twice a month. Non- fasting days should ultimately involve healthy caloric intake.

  • Choose your day fasting. As the name implies, fasting days are based on choice and preference.
  • Overnight fasting. This is the simplest approach out of all the different forms. It usually involves an overnight fasting window of 12 hours.

Evidence of fasting from animal studies

Generally, multiple animal studies highlight the positive outcomes associated with fasting and metabolic syndrome, this though does not ameliorate the fact that variable results have been obtained in specific results in connection with intermittent fasting. In certain studies, specific fasting types yielded optimum results while others didn’t. Also, some studies revealed the intricacies of certain factors in further determining the outcomes of fasting on animals, most especially rodents.

For example; in rodents, numerous studies observe that intermittent fasting yields significant results by completely reversing and preventing metabolic syndrome, furthermore, blood pressure and inflammation are reduced with an increment in insulin sensitivity. This directly affects the nervous, neuromuscular, and cardiovascular systems of these rodents by improving them.

In diabetic rodent models, hyperglycemia is alleviated and the heart is preserved from ischemic damage.

Rats and mice on fasting diets experience less neuronal degeneration and lesser clinical symptoms in models of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.

For aging, alternate day fasting has variable effects on rodents, depending on age and species of rodents. In some species of rodents, fasting increases lifespan to about 80% while it has adverse effects in other species.

For cancers, alternate-day fasting caused a reduction in the occurrence of lymphomas in rodents; another study revealed one day a week fasting delayed spontaneous tumorigenesis in mutant mice (specifically p53 deficient mice). On the other hand, however, a study revealed the carcinogenic effect of fasting on mice, the mechanism being due to the reduction of glucose, IGF-1 and insulin caused cellular atrophy in tissues such as the liver and kidney this reduction caused a resultant cellular proliferation during refeeding which when combined with carcinogens had a tumorigenic effect.

Evidence of fasting from human studies

Fasting and its effect on metabolic syndrome have been widely studied in humans with the outcomes generally being positive. Fasting in humans improves insulin sensitivity, stimulates lipolysis, and combats high blood pressure.

Body fat and blood pressure were reduced and glucose metabolism improved in obese subjects in response to an alternate day modified fast (Klempel et al., 2013; Varady et al., 2009). Overweight subjects maintained for 6 months on a twice-weekly Intermittent fasting diet in which they consumed only 500–600 calories on the fasting days, lost abdominal fat, displayed improved insulin sensitivity, and reduced blood pressure (Harvie et al., 2011). Subjects undergoing coronary angiography who reported that they fasted regularly exhibited a lower prevalence of diabetes compared to non-fasters (Horne et al., 2012). These all pinpoint the positive effects of fasting on the body in connection with metabolic syndrome.

Several controlled human studies conclude that fasting done with a vegetarian diet (and maybe with other modified diets) provides substantial effects in the treatment of rheumatoid arthritis. There have been little to no human studies on the effects of fasting on neurodegeneration and the prevention of cancer; data obtained is usually inferred from animal studies.

Evidence of calorie restriction from human & animal studies

A clinical trial of humans was undertaken to determine the effects of an alternate day calorie restriction regimen on overweight adults with moderate asthma. For this clinical trial 10 subjects with BMI greater than 30 were maintained on ad libitum every other day while they consumed 20% less of their normal calorie intake on intervening days for 8 weeks. Nine of the subjects adhered to the diet and lost about 8% of their initial body weights. After two weeks of the study, it was observed that asthma-related symptoms improved and PEF levels soared. Beta-hydroxybutyrate levels increased while leptin levels reduced, this indicated the metabolic model of the body, i.e., the body utilised non-hepatic energy sources (free fatty acids, ketone bodies, etc.). This resulted in decreased levels of triglycerides, LDL, and cholesterol, also there was a significant reduction in markers of oxidative stress such as 8-isoprostane, nitrotyrosine protein carbonyls, etc., and indicators of inflammation such as tumour necrosis factor & brain neurotrophic factor with a resultant increment in antioxidant uric acid.

Another study and the first clinical trial to study the sustained effects of calorie restriction on human calories was conducted in 2 phases and lasted for 2 years.

Many deductions were drawn from this clinical trial, for the cardiometabolic risk, it was deduced from phase 2 of the trial that 2 years of moderate calorie restriction reduced numerous metabolic risk factors in young non-obese adults. This finding paves a way for future long-term population health benefits.

In several mammal studies especially in rodents, calorie restriction has been found to have positive outcomes on metabolic risk and longevity. It also protects against cancer in many mouse tissues by altering age-associated shrinkage of telomeres, therefore reducing the incidence of tumours in mice that overexpress telomerase. Some positive outcomes associated with caloric restriction occur as a result of the upregulation of cellular and molecular defense systems.

Two different researches conducted by different organisations on rhesus monkeys in connection with calorie restriction yielded two different results in connection with survival. One of the research undertaken by the University of Wisconsin found that rhesus monkeys that were maintained on calorie-restricted diets contained 30% lower calories than the control group aged more than the average for primates in captivity. The NIA on the other hand found no significant effect of calorie restriction on the aging of the rhesus monkeys. Data from both research parties however highlighted the effect of calorie restriction on age-related diseases; there were lower incidence of age-related diseases in rhesus monkeys that were on calorie-restricted diets as compared to the controls.

(Article by: Dr. Thiago Freire and Lois Wussah)