Caloric restriction


In 1935, a study on caloric restriction in mice provided evidence, for the first time, that such an undertaking can promote longevity and disease fighting ability in mammals1.  Until then, only studies on yeast and lower animals had been completed in this area of research.  The novelty of the mouse study soon wore off, however, and the findings were not revisited until some time in the late 1980’s / early 1990’s, when interest in caloric restriction was renewed.  At that time, scientists wondered if the effects would be similar in primates, and, as a result, in humans.

Longitudinal studies using primates were soon underway, and now, nearly three decades later, the results look promising.  The primates of choice, for most undertakings, were (are) Rhesus monkeys.  Rhesus monkeys have a lifespan of approximately 35 to 40 years, making them easier to study, in terms of longevity and disease development, than higher primates such as chimpanzees or humans, whose lifespans are generally twice as long.

Research using mice, and a host of other species, continued alongside primate studies in an effort to accumulate as much comparable data as possible.  Yeast research has also continued, in most part due to striking working mechanism similarities that seem to span across all species studied thus far.

The question on everyone’s mind was “will caloric restriction have the same effect on all species studied?”.   An affirmative answer would strongly suggest the same to be true of humans.  Indeed, this is precisely what research to date has determined:  all species studied thus far have reacted in much the same way to caloric restriction.  Human studies following these findings have also yielded promising results.

CALORIC RESTRICTION DEFINED

Caloric restriction should not be confused with, or lead to, malnutrition.  Two types of caloric restriction have been identified to have an effect on aging and disease:  transient and sustained caloric restrictions.   Moderate and pronounced caloric restrictions have been found to improve health and longevity.

Transient caloric restriction refers to short-term restrictions that occur once, or several times, over the course of the lifespan.   Sustained caloric restriction involves a drop in daily caloric intake from the onset of the study through the end of the subject’s life.  Of these, sustained, pronounced caloric restriction has been found to have the greatest positive impact on disease prevention and longevity.

Moderate caloric restriction entails a reduction of daily caloric intake by 15% to 17%, whereas, pronounced caloric restriction involves a reduction of approximately 30%.  In terms of human caloric needs, 30% less calories would translate into a reduction of approximately 700 calories per day for a healthy adult whose BMI is in the recommended range and who normally consumes 2,500 calories daily, leading to a total caloric intake of 1,800 per day. 

TRANSIENT CALORIC RESTRICTION AND CANCER RISK

Transient caloric restriction studies are scarce, yet, they are as important as sustained restriction studies because the former is the most likely to be implemented by people over the course of their lives.  While most people have difficulty maintaining sustained caloric restriction for the entirety of their lifespans, many have dieted over the courses of their lives, and some have repeatedly engaged in “yo-yo dieting”, the latter having been shown by recent studies to be most likely to have detrimental effects on overall health.

The Dutch famine of 1944 – 1945 has been the subject of a number of studies on transient caloric restriction and its long term effects, in most part because the subjects were human. The first studies of the Dutch famine had surprising results (which more recent studies have since replicated).  Unlike sustained moderate or pronounced caloric restriction, transient restriction emerged as a risk factor for breast cancer later in life.  In addition, women who were exposed to the famine as children experienced subsequent reproductive difficulties.

This discovery prompted researchers to attempt replicating the findings using animal models.  They were not disappointed.  Studies in mice have repeatedly shown that while sustained caloric restriction works wonders against cancer onset and development, transient restriction has the opposite effect.  A study on the influence of underfeeding during the “critical period”, or thereafter, on carcinogen-induced mammary tumors in rats, concluded that transient restriction followed by ad libitum feeding could lead to increased cancer risk.  Another similar study by Kritchevsky on the promotion phase of cancer development found that not only was the risk of cancer increased in the wake of transient caloric restriction (“yo-yo dieting”), but that the study subjects gained a disproportionate amount of weight, very quickly, once the restriction was lifted3.

SUSTAINED CALORIC RESTRICTION AND CANCER RISK

Another 2002 study on the effects of sustained caloric restriction in mice found a 60% reduction in the number of precancerous intestinal polyps in mice at high risk for gastrointestinal cancers4.  The same study found that mice consuming a diet high in fruits and vegetables had 33% fewer polyps that the control mice, suggesting that even moderate caloric restrictions have a positive effect on the reduction of tumor formation.

A longitudinal study on Rhesus monkeys which began in 1989 at the Wisconsin National Primate Research Center (WNPRC) is perhaps one of the most telling in that it documented not only the effects of sustained caloric restriction on cancer, but on longevity and overall health of the subjects.  The photographic account/evidence of physiological changes is most striking1.

The Rhesus monkeys who participated in the WNPRC study generally have a lifespan of about 27 years.  All animals were adults when the study began (the results of which are a testament that it is never too late to impact the outcome of one’s life), ranging in ages from 7 years to 14 years.  Over the course of a six month period, the caloric restriction group (CR group) was slowly acclimated to a 30% decrease in daily caloric intake.  The CR animals maintained this level of caloric intake for the remainder of their lives.

Age related diseases in Rhesus monkeys had been well documented at the WNPRC and are very similar to those of humans’.  They include cancer, cardiovascular disease, and diabetes.  Over the course of the study, the CR animals experienced a decrease in body weight while maintaining a healthy BMI, thus, reducing their risk for obesity, which, in turn, is a risk factor for cancer.  Furthermore, they consistently experienced improved metabolic function, specifically, insulin sensitivity.  The incidence of cancer, which normally increases with age in Rhesus monkeys, was reduced by 50% in the CR group (as was the incidence of cardiovascular disease, also by 50%).  The biological age of the CR group monkeys became significantly younger than that of their cohorts in the control group.  A similar effect has been found in studies of people on long term CR1.

MECHANISM OF ACTION

Restriction of calories stresses the organism resulting in a response by DNA repair enzymes and apoptosis (programmed cell death) which protect the body from environmental insults.  “[The] proliferation of cells is reduced with both increased rates of apoptosis together with decreased DNA synthesis and increased DNA repair, limiting the number of preneoplastic lesions. Oxidative stress is reduced, resulting in decreased reactive oxygen species that can damage DNA. Furthermore, of interest to hormone associated tumours, levels of a number of hormones and growth factors are altered during caloric restriction: glucocor- ticoids are increased whereas concentrations of IGF-I (and to a lesser extent IGFBP-3 resulting in decreased bioavailability of IGF-I), insulin, prolactin, estrogens and leptin are decreased.”3.

A DNA transcription factor called heat shock factor 1 (HSF1), which is regulated by the enzyme sirtuin 1 (SIRT1), exists as a monomer in unstressed mammalian cells.  It responds to stresses such as the free radicals that play a role in carcinogenesis by resolving damaged, misfolded, and aggregated proteins.  As we age, the amount of SIRT1 protein decreases and HSF1 concentration increases.  Sustained caloric restrictions has been found to cause overexpression of SIRT1, which, in turn, enhances the ability of cells to survive prolonged exposure to heat shock temperatures.  SIRT1, therefore, functions as a positive cofactor of HSF1 and enhances the heat shock response5.

The discovery that caloric restriction is beneficial has been publicized in the main stream media for many years, albeit not as heavily as it deserves to be. Public reaction has generally been positive, yet, as expected, no sustained efforts to adopt lower calorie lifestyles have been observed in the general population.

In the West, where high calorie foods are stocked in great proportions on supermarket shelves and fast food restaurants pepper the landscape in astronomical numbers, temptation is unavoidable.  It is around every corner, invading our homes, workplaces, and cars via the airways, with corporate advertisements designed to entice and titillate, all of which are backed by significant market research into what people like and what works best to get them pining for the goods on display.  Few people stand a chance, and fewer yet are aware of the impact such advertisements and supermarket food displays have on us. Most of us are convinced that such things do not sway us, yet our collective Western girth seems to indicate otherwise.

Complicating matters is the average person’s upbringing and dietary habits that follow and impact our lives since before we are born.  According to recent studies, an expectant mother’s dietary choices can influence her unborn child’s future eating habits and overall health2.  High fat, high calorie food exposure in the womb can adversely affect the development of normal leptin balance in the fetus and can predispose the child to calorie rich food cravings that eventually result in life long weight and related health problems.  Adding insult to injury, most parents will feed their children the same kind of unhealthy diets that they themselves consume, further ensuring that poor dietary habits become engrained and more difficult to break later on.  Many still believe that being plump and cherub-like are desirable qualities in small children and often insist that children finish everything on their plates.

A reduction in caloric intake generally requires a significant change in food choices.  A person accustomed to eating a diet heavy in processed foods, meats, and dairy would have a fair amount of difficulty reducing caloric intake while at the same time continuing to enjoy these foods and not be left feeling hungry.  Reduced caloric intake without a life-long struggle against hunger can only be achieved by adopting a Mediterranean, vegetarian, or vegan life style.  Since most people are unfamiliar with these kinds of eating styles, they often assume they would feel hungry or deprived and opt not to try.  Some who attempt to make significant changes are ill prepared to do so and usually revert to their old, familiar ways.

BOTTOM LINE

That caloric restriction has a positive effect in the prevention of cancer, degenerative diseases in general, and on the extension of lifespan is difficult to dispute.  The overwhelming evidence suggests it is a plausible tool for prevention and, as is the case for diabetes and heart disease, an effective tool in the treatment of a number of illnesses.  Implementation of sustained, pronounced caloric restriction, however, is difficult because most people do not have the tools (psychological and practical) to make such a lifestyle change a permanent one.  Sustained, moderate caloric restriction stands a better chance of implementation and sustainability, however, it is a viable option only when coupled with education (i.e. cooking methods, shopping habits, family support).

Transient caloric restriction is perhaps the most likely to be adopted by most people, however, there are risks involved in choosing this path that may outweigh the benefits.  Transient caloric restriction followed by a return to “normal” feeding habits has been shown to be detrimental to health and to be a risk factor for cancer.  This kind of dietary restriction, commonly known as “yo-yo dieting” is not recommended, and is particularly dangerous for persons who already have cancer.

REFERENCES

  1. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R.  Caloric restriction delays disease onset and mortality in Rhesus monkeys.  Science 2009;  325:201-204.
  2. Wellcome Trust (2008, July 1). Poor Diet During Pregnancy May Have Long Term Impact On Child’s Health, Study Suggests. ScienceDaily. Retrieved November 23, 2009, from http://www.sciencedaily.com­ /releases/2008/06/080630200951.htm
  3. Elias SG, Peeters PHM, Grobbee DE, van Noord PAH.  Transient caloric restriction and cancer risk (The Netherlands).  Cancer Causes Control 2007; 18:1-5.
  4. Federation Of American Societies For Experimental Biology (2002, April 25). Even Moderate Caloric Restriction Lowers Cancer Risk In Mice. ScienceDaily. Retrieved November 24, 2009, from http://www.sciencedaily.com­ /releases/2002/04/020424073022.htm
  5. Saunders L, Verdin E.  Stress response and aging. Science 2009; 323:1021-1022
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