Calorie restriction dieting

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CR and cancer prevention

The accumulation of multiple DNA mutations generates a complex multistage disease: cancer. The mutations lead deregulation of cell differentiation and proliferation. Endogenous protective enzymes and molecules can, however, prevent cancer. CR is an effective intervention for protecting mammals against these diseases since it, among others, reduces growth and inflammation in normal and precancerous cells and induces the apoptosis in damaged cells.

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Figure 3 : CR mechanisms to prevent cancer (V.D. Longo et al, 2010)

The mechanism of CR to prevent cancer is using the same sensory sensors as previously shown. Figure 3 suggests three scales about organism adaptations: metabolic, molecular and cellular. This part of the report is more focused on the cellular adaptation. These modifications induce the increase of DNA repairs, stress resistance, removal damage cells, antioxidants genes, and protein turnover, etc. Adaptive mechanisms working together limit the incidence of cancer. A study carried out on monkeys shows that the group which received the 30% CR diet reported a reduction of 50% in the incidence of cancer. However, scientists argue that results depend on the CR severity, on the genetic backgrounds of the animals and on the age when CR is commenced. Furthermore, the effects are non-homogenous among the different cancers and are type-depending. Previous studies have hypothesized that physiological response in human should be similar to those in rodents and monkeys with long-term effects. (V.D. Longo et al, 2010)

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Others effects relating health

Comprehensive Assessment of Long-term Effect of Reducing Intake of Energy (CALERIE) phase 2 research point out psychological well-being affected by long-term CR on nonobese adults. The parameters examined were the weight, the mood, the quality of life, sleep and sexual function. Standard calorie intake was reduced by 25%. The result proves that 24 months of CR is marked by an average of 10% weight loss, an improvement in health in general and in the mood, a reduction of tension, an enhancement of sexual drive and relationship. Moreover, people found that they sleep better since the twelfth month, CR might mitigate changes in sleep that happen with age. Accordingly to these results, no negative effects of long-term CR diet has been shown, solely some positive one (C.K. Martin et al, 2016). J. Most et al (2016) show that no damage was reported on mental and psychological capacity and cognitive performance, attention, memory are not affected by a 25% of CR during 6 months. Moreover, CR participants have reduced apprehensions about body weight and have been disinterested concerning food. In conclusion, several benefits on the health have been highlighted.

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Excessive calorie restriction

It has been shown that severe calorie restriction leads to significant harmful effects. For instance, one study has been conducted on lean men, standard calorie intake was decreased by 45% for 24 weeks. These persons reported anemia, depression, and irritability, lethargy, neurologic deficiency, weakness, muscle wasting, etc. Afterward, scientists conclude that it is almost impossible to define a safe universal threshold of calorie restriction. Several factors impact such as the daily energy exertion, duration of calorie restriction and the initial body composition. Then, in order to evaluate the safety of CR, one consideration can be done: the estimation of BMI (Body Mass Index). Furthermore, the ideal diet, which is combined with optimal health, is often unknown. (L. Fontana et al, 2007; J. Most et al, 2016)

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Final remarks and perspectives

In order to counteract age-associated diseases as type 2 diabetes and cardiovascular diseases, it is possible to use calorie restriction mimickers. For the last few years, different pharmacological agents emerged with similar effect as CR. Their aptitude to raise the oxidative metabolism turnover by the action of AMPK/SIRT1 axis and the inhibition of TOR have been investigated. Resveratrol is the most powerful one. It reduces secretion and insulin level and then raises insulin sensitivity. Moreover, resveratrol enhances oxidative phosphorylation and mitochondrial biogenesis, reduces fat mass, triggers sirtuins action by a higher NAD+ /NADH ratio. Thus, thirty days of treatment with resveratrol in obese people launch AMPK, sirtuins and therefore enhance respiration of muscle mitochondrial founded on fatty acid. Others composites have been studied such as rapamycin, an inhibitor of TOR, metformin which is use clinically for the treatment of type-2 diabetes. (G. López-Lluch et al, 2016)

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Future studies

CALERIE is the most complete study which has been done on humans. It has started few years ago and the result shows that CR increases insulin sensitivity. However, just few persons have been tested so it is actually difficult to reach any conclusion. Moreover, the effects observed can have been influenced by a better quality of the diet (G. López-Lluch et al, 2016). Therefore, further studies need to be investigated to figure out the effects of CR on human, interaction among CR, diet composition, psychological factors on metabolic, exercise and molecular pathway. Moreover, investigation of CR mechanism may apprehend human discords as Alzheimer’s disease. Then, people might try to practice CR to increase health and lifespan. Nevertheless, excessive calorie restriction leads to a lack of nourishment and has negative clinical effects. (E. Cava et al, 2013; L. Fontana et al, 2007)

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Conclusion

Calorie restriction is the most studied experimental intervention for extending lifespan and health span. This process slows aging and increase average and maximal lifespan because it provides a higher protection against the oxidative stress by the proliferation of efficient mitochondria. Moderate calorie restriction protects from the major causes of morbidity and mortality as type 2 diabetes, hypertension, cardiovascular diseases, inflammation and the development of obesity (E. Cava et al, 2013). The antioxidants activity is species-dependent, age-dependent, and organ-dependent.

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References