Calorie Restriction Improves Cell Function

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Calories consumed don’t just impact a number on a scale.

Researchers from the University of São Paulo (USP) have found that meals with fewer calories may protect cells from some diseases. Results of this research were presented the first day of the São Paulo Research Foundation's (FAPESP) FAPESP Week London that occurred February 11-13, 2019.

FAPESP funded some of the research under the Center for Research on Redox Processes in Biomedicine. Alicia Kowaltowski, a professor at the USP Chemistry Institute states, “"We are looking at how changes to the diet affect metabolism and how that ends up changing the odds of having diseases associated with aging,"

An experiment conducted on mice by the group highlighted how a reduced-calorie diet may protect the brain from cell death linked with Alzheimer’s, Parkinson’s, epilepsy, and stroke. To carry out the experiment, mice were divided into two groups. In the first group, the scientists estimated the average number of calories the mice would consume without calorie restrictions. They fed the second group 40% fewer calories. Then the mice in the two groups were given a shot that contained a compound known to cause seizures, damage, and neuronal cell death after 14 weeks.

The researchers discovered that the group without caloric restrictions had seizures while the animals with caloric restriction did not.

The scientists then investigated in vitro. Organelles of the brains of the mice were isolated and divided into two groups: those with an unrestricted diet and those with reduced-calorie diets. Calcium was then added to the medium. The researchers found that calcium uptake was better in the mitochondria in the calorie-restricted group.

Energy generation in cells is controlled by mitochondria. Mitochondria in the mice on a calorie-restricted diet had increased calcium uptake ability in cases where the level of calcium was unusually high.

Limiting calories has been found to improve pancreatic cell response to higher levels of blood sugar. This conclusion was reached after doing experiments utilizing beta cell cultures of pancreatic islet cells needed to produce insulin.

Blood serum from mice placed on a variety of diets like the study on the effects of reduced calories on neurons were utilized to feed the cells produced in vitro.*

Scientists question whether the phenomenon is due to mitochondria, as insulin secretion is dependent on the presence of adenosine triphosphate (ATP, the compound that stores energy) in the cell. When oxygen consumption was measured by the two groups of cells, scientists noted that it was increased in cells that were treated with serum from animals with calorie restrictions. As respiration is the cause of insulin release during peak glucose, this data showed that the cells produced more ATP when the animals were subjected to calorie restrictions.

Other studies indicate that cell mitochondria treated with serum from calorie-restricted animals exchanged more material with each other, making them more efficient.

"Understanding how metabolism works is vital for preventing and treating metabolic conditions like obesity," states Kowaltowski. She notes that obesity is a key prognostic factor of unhealthy aging. "Obese individuals are much more likely to have age-related diseases. This includes neurodegenerative diseases like Alzheimer's, proliferative diseases like cancer, and metabolic diseases themselves, such as Type 2 diabetes, hyperlipidemia, heart attack, and CVA. Obese people have a higher incidence of all of these."

These diseases can largely be prevented by preventing obesity. Despite constant warnings about the need for balanced nutrition and exercise, the global obesity epidemic has not declined. Kolaltowski added “If we try to understand the mechanisms through which obesity increases those diseases, we will have more tools to fight and prevent them.”

While weight control is a common problem for many, dietitians can help their clients prevent obesity with the following tips:

  1. Focus on fiber. Encourage whole grains over refined grains, whole fruit over juice, and increased vegetable consumption. Fiber is filling, which may lead to reduced overall food intake.
  2. Reduce animal-based protein. Meat and dairy products tend to be higher in fat and calories than plant-based alternatives such as beans, lentils, and plant-based milks.
  3. Limit sugar intake. Refined sugar from soda, candy, and high-calorie desserts lead to weight gain when consumed regularly.
  4. Encourage water over sweetened beverages, specialty coffees, or sports drinks.
  5. Encourage exercise for stress relief. Stress eating, eating due to boredom or anything other than hunger may lead to unwanted weight gain and a poor relationship with food. Talk with clients about how they deal with stress or refer them to psychologists or counselors for more help.

*Insulin excretion through beta cells was normal in the cells treated with serum from calorie-restricted animals, low when blood glucose was low and elevated when glucose was high. The same was not the case in animals that consumed more calories and became obese. The researchers believe that there may be a circulating blood factor that changes beta cell function acutely.

By Lisa Andrews, MEd, RD, LD


  1. Fundação de Amparo à Pesquisa do Estado de São Paulo. "Diets consisting of fewer calories improve cell performance." ScienceDaily. ScienceDaily, 12 February 2019. <>.
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