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Calorie Restriction Effects on Biomarkers of Health and Longevity in Humans

By Edited Apr 21, 2016 0 0

We’re all familiar with the signs of aging: gray hair, wrinkled skin, new prescriptions for reading glasses and/or hearing aids. There are also the loss of muscle tone and bone mass which progressively worsen as the years pass. These are known officially as “primary aging”. There is also “secondary aging” which includes noncommunicable diseases, poor diet, lack of exercise, and smoking. Slowing down aging is all the rage both due to vanity and to a basic desire to improve the quality and length of life.


Research looking at longevity is much easier to accomplish in critters that don’t live as long as humans. Thus, most studies are done on fruit flies and rodents. The problem is that human biology is different than that of fruit flies or rats. For example, we humans are vulnerable to ischemic heart disease which is not an issue in rats. Therefore, studies on fruit flies and rats can only point to points of interest when doing human studies.


Rodents allowed to lounge around and eat at will tend to get fat and continue getting fatter as they age. Many studies have shown that lean rodents live longer than fat rodents. A number of studies have shown that calorie restriction alone, calorie restriction with exercise, or exercise alone all help reduce body fat stores. Being able to maintain leanness could be one key mechanism through which Calorie Restriction with Optimal Nutrition (CRON) works to extend life span. In this context, CRON appears to be a viable method of lengthening life span.


Interestingly, rodents who stay lean through exercise alone only increased their average longevity. Those rodents that also restricted their calories showed an increase in both average and maximal longevity. So, HOW they remained lean was an important factor in the results they experienced. Whether or not that is true for humans is unknown. The adaptive response mechanism that sets CRON apart from exercise in slowing primary aging is currently a subject of controversy.


Some researchers suggest that mechanism of CRON is linked to white adipose tissue and the production of adipokines. Calorie restriction affects fat mass including white adipose tissue. Adipose tissue secretes cytokines or more correctly adipokines such as adiponectin and leptin. Increased adipose tissue is correlated with the pathogenesis of certain cancers (e.g., colon, breast, endometrial, kidney, and pancreatic) due to adipokine production, insulin resistance, hyperinsulinemia, and chronic inflammation.


Since both exercise and calorie restriction reduces adiposity, including visceral fat, this still does not explain why calorie restriction works better than exercise for increasing life span. One possible answer is that exercise, in contrast to CR, causes an increase in muscle insulin sensitivity and responsiveness but why this would make a difference is not yet clear. More likely, the answer is that CRON is more effective than exercise in mobilizing stores of visceral adipose tissue.



Heart disease is a major cause of death especially in developed countries. Two groups of individuals who used CRON over a period of time were found to have improved their cholesterol readings except that one group had very low “good cholesterol” while the other had very high “good cholesterol”. Noting that the former group had a nutrient balance of 10% fat, 76% carbs, and 14% protein and the latter group had a balance of 28% fat, 46% carbs, and 26% protein, the resulting question is “which number lead to the better HDL (good) cholesterol reading? Some believe it is the fat percentage but at this point that is just speculation.


Another major cause of death in industrialized nations is cancer. The lifestyles of such nations -- high calorie/protein consumption, low physical activity, and greater adiposity – are obvious possible causes. Obesity is also linked to other cancer risks factors such as hyperinsulinemia, elevated plasma insulin-like growth factor (IGF-I), higher bioavailability of steroid sex hormones, and systemic inflammation. There are other factors for sure. As the studies included in this review have demonstrated, CRON is an excellent way to not only reduce adiposity but also reduces these other risk factors for cancer.


Fasting glucose and insulin sensitivity have been linked in rodent studies as biomarkers which affect longevity. Studies looking at CRON using alternate day fasting found mixed results-worsened fasting glucose but improved insulin sensitivity. The studies did not include many subjects nor were they of sufficient length which leaves many questioning the usefulness of the results. Hopefully there will be better studies in the future.


That last sentence should signal in you a precautionary thought. While there is evidence that CRON is beneficial that evidence is in its infancy. We are so far away from being about to say much with total confidence in nutrition. Clearly, eating more calories than we need is unhealthy. Whether eating a percentage below our basic needs will lengthen our lives is unknown and then there is the question of just how much below our baseline must we eat in order to add years to our life? No one knows that. Eat at or below your baseline to the degree you can comfortably do so without stealing quality of life in the name of quantity of life.



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