~Fasting and Calorie Restriction, Part 2 - CRON

~Fasting and Calorie Restriction, Part 2 - CRON
CRON (Caloric Restriction with Optimal Nutrition) -
With Dietary and Supplemental Suggestions To Increase Life Span
  • Animal Studies Yield Valuable Data
  • Calorie Restriction and Oxidative Stress
  • Calorie Restriction and Dementia
  • Calorie Restriction Benefits Diabetics
  • How the Immune System Responds to Calorie Restriction
  • Calorie Restriction and Malignancies
  • Effects of Calorie Restriction on p53, IGF-1, and Leptin
  • Explanatory Comments
  • Calorie Restriction and the Heart
  • Convincing Summation
  • Interventions To Support Longevity
  • The Glycemic Index and Glycemic Load
  • Supplements to Emphasize in Resisting Age-Associated Debility
Claims that various nutritional interventions can extend life span are manifold, but some are grounded in greater credibility than others. Among regimens debated, gerontologists often agree that Caloric Restriction with Optimal Nutrition (CRON) offers the greatest likelihood of succeeding.

The concept was first introduced in the early 1900s, but Clive McCay (Cornell University) advanced the theory significantly when (in the 1930s) he found that calorie-restricted rats lived longer than those allowed to eat ad libitum. Though the exact mechanisms whereby dietary restriction retards aging and extends life span are still not fully understood, much of the emerging data suggest that McCay's calorie-restricted rodents lived longer and aged more slowly because they were more resistant to stress and their cells appeared protected against damaging agents (Van Remmen et al. 2001).

Some of the greatest contributions substantiating CRON are ascribed to Roy L. Walford, M.D., who has devoted most of his life to validating the theory. Dr. Walford "practices what he preaches" as demonstrated by his 2-year BioSphere II experiment, during which he and seven others lived on a calorie restricted diet. The Biospherians were forced to eat a calorie- restricted diet for two years because they were unable to grow enough food to sustain them at a normal level. Dr. Walford (of UCLA Medical Center) was well versed in calorie restriction and guided the group through the experience.

The eight people in the BioSphere study averaged 1,800 calories per day during the first 6 months, increasing to 2,200 calories per day by the end of 2 years. In the first 6 months, body weight dropped an average of 15%, blood sugar dropped 20%, blood cholesterol dropped 38% and blood pressure dropped significantly (30% systolic and 27% diastolic); white blood cell count dropped 24% (Walford 1988, 1994; Best 1995).

The results obtained from the BioSphere II experiment are consistent with information gathered from ongoing animal studies conducted at the National Institute on Aging and the University of Wisconsin (Madison). For example, monkeys (calorie restricted) weighed less and had less body fat. They exhibited lower body temperature, as well as lower fasting blood glucose and insulin levels; insulin sensitivity increased. Typically, the monkeys also had lower blood pressure, reduced triglyceride and cholesterol levels as well as increased levels of HDL2B (low levels of this HDL subfraction are associated with increased cardiovascular disease in humans) (Lane et al. 1999).

According to Ben Best, a CRON advocate, "From an evolutionary or survivalist point of view, many of the observed effects of CRON make a great deal of sense." When food is abundant an animal grows large, matures quickly, and reproduces. When food is scarce, less energy is devoted to growth, basal metabolism, or reproductive capacity. Energy is maintained for muscular action, which is most important for survival.

Adult male rats with 50% caloric restriction show a 42% drop in serum testosterone and a 29% drop in luteinizing hormone (LH). Female adult rats also show a drop in LH but follicle-stimulating hormone (FSH) increases. Puberty is delayed in both pre-pubescent males and females, and fecundity (fertility) is reduced after puberty; irregularities in estrus cycles were correctable, however, by re-feeding (Best 1995).

Dr. Walford found that previous attempts to apply CRON to adult animals often did not succeed (and in fact resulted in a shorter life span) if the restrictions were applied too rapidly. CRON produces the greatest extension of life span when started just before puberty, but the result is a smaller animal. Applying CRON just after maturity, Dr. Walford was able to achieve roughly 90% of the extension of both average and maximum life span without the stunted growth (maximum life span denotes the longest any member of the species has ever lived). If animal studies prove equally applicable to humans, a 60% calorie restriction could produce roughly a 50% increase in mean and maximal life expectancy from whatever age the program is begun. A 10% caloric restriction could produce approximately a 25% increase in life expectation. Dr. Walford believes that even a person between the ages of 50 and 60 could experience a 10- to 15-year life extension with CRON (Walford 1988, 1994; Best 1995; Bozhkov 2001).

Animal Studies Yield Valuable Data

The CRON theory has been most studied in lower species but the underlying principle has extended to include long-lived primates. To determine if calorie restriction has similar actions in higher species, the National Institute on Aging (NIA) initiated a study in 1987 to investigate the effects of a 30% caloric reduction in male and female rhesus macaques (Macaca mulatta). Comment: Rhesus monkeys living in captivity can live to be about 40 years old. At the genetic level, Rhesus macaques and humans are nearly the same, sharing a genome that is more than 90% identical (Devitt 1998).

The NIA study demonstrated that calorie restriction decreases body weight and fat mass, improves glucoregulatory function, and decreases blood pressure, blood lipids, and body temperature. Juvenile males exhibited delayed skeletal and sexual maturation, and later were able to overcome an age-associated decline in both dehydroepiandrosterone (DHEA) and melatonin; bone mass was unaffected in both males and females. Eighty-one percent of the monkeys in the NIA study are still alive, suggesting that calorie restriction may have beneficial effects on morbidity and mortality statistics (Mattison et al. 2003).

Although often censured, mice studies are valuable in assessing the worth of therapies to increase life span. Different strains of mice live variable amounts of time (some live considerably longer than others but most murine life spans are measured in months rather than years). For example, the typical SAMP8 mouse (genetically prone to undergo accelerated aging) has a life span of only about 12 months. By extending the life span (and improving the mental health) of SAMP8 mice, the merits of calorie restriction can be more rapidly studied. Few individuals of this generation are willing to forgo information that might extend their years of healthy living, waiting for data to accumulate regarding primates undergoing calorie restriction.

For example, Dr. Richard Weindruch (University of California-Los Angeles) reports that he and his team of researchers have been able to extend the average life span of long-lived strains of mice to 45 months from 32 months and increased by 34% the maximum life span to 53 months from 40 months through calorie restriction. Overall tumor incidence was 78% in the control group vs. 38% in the calorie-restricted group. In addition to living longer, the mice consuming fewer calories stay "younger longer" than do controls as judged by many age-sensitive biologic parameters (immune system aging, eye lens proteins, liver enzyme activities, and learning and behavioral patterns). Since calorie restriction can prevent the diseases of aging, maintain health and youthfulness in animals at advanced ages and extend maximum life span in mice and rats (up to the equivalent of 160 years in humans), it is now acknowledged by scientists as a valid way of slowing aging in mammals (Weindruch 1986; UW-Madison Institute on Aging; Kent 2003).

Thus, scientists have been aggressively searching for quicker methods of measuring the rate of aging in humans (biomarkers of aging). Since genes control every aspect of biological life (including health, senescence, and longevity) and caloric restriction extends healthy life span, a rational approach to finding biomarkers of aging is to compare gene expression in normal aging animals with gene expression in calorie-restricted animals (a heretofore slow, labor intensive, and costly pursuit).

A tremendous breakthrough occurred when scientists at the University of Wisconsin used high-density DNA microarrays (gene chips), a technology developed by Affymetrix (Santa Clara, California) to rapidly detect expression in up to 6,347 genes at one time. When researchers (Richard Weindruch and Tomas Prolla) compared gene activity in normally aging mice with gene expression in calorie-restricted mice, they found that many of the genetic changes of aging were reversible by calorie restriction (Lee et al. 1999).

Scientists at Biomarker Pharmaceuticals, a company funded (to date) exclusively by The Life Extension Foundation, dramatically advanced the model when (after studying 1200 genes) it was determined that the positive response of an animal to calorie restriction is much quicker than once theorized. It was previously thought that calorie restriction would have to be applied over the lifetime of the animal to be of significant advantage. Instead, it was determined that 70% of the changes in gene expression (caused by over a two-year calorie restricted regimen) occurred in only two to four weeks after placing mice on a calorie restricted diet. As Biomarker scientists established that even "senior" rodents realized about a 40% extension of life span when undergoing a calorie-restricted diet, rodents of all ages became candidates for life extension through caloric restriction.

Biomarker scientists also found that some genes increased in expression (including those associated with inflammation and stress proteins) while in other instances, gene activity decreased as the animal aged. Recently, scientists have shown that a single gene can control both life span and the timing of systemic and cellular aging in mammals, indicating only a few pivotal genes may be intricately involved in longevity.

For example, unlike calorie-restricted mice, long-lived Snell dwarf mice ate all they wanted, became obese and exhibited higher levels of leptin (a hormone derived from fat tissue). Researchers are aware that the Pit1 gene produces dwarfism in Snell dwarf mice as a result of impairments in the pituitary, the master gland. These impairments result in deficiencies of three hormones: thyroid hormone, growth hormone, and prolactin. Thus, it appears that the life extension mechanism may rely on deficiencies of one or more of these hormones. Some researchers believe that a deficiency in the growth hormone may be the most interesting of the three in explaining longevity (recall that insulin-like growth factor-1 (IGF-1) is made in response to growth hormone) (Premo 2001; Kent 2003). To read more about IGF-1 consult the section entitled The Effects of Calorie Restriction on p53, IGF-1, and Leptin appearing later in this protocol.

When the exact genes that govern aging are pinpointed, scientists will be able to target those genes, the proteins they produce and the biologic mechanisms they affect in order to develop new drugs and other therapies to slow aging, prevent disease, and extend healthy life span (the screening techniques used at BioMarkers to assay anti-aging drugs are 25 times faster than any other methods presently used). Comment: The current best estimate of the number of genes in the human body is 24,847. Many scientists think the estimated gene tally will eventually rise, perhaps to above 30,000 (Pearson 2003).

Calorie Restriction and Oxidative Stress

Researchers at the University of Texas Health Science Center (San Antonio, Texas) recently reported that accumulating evidence strongly suggests that oxidative stress underlies the aging process. The researchers also found that senescence can be forestalled by calorie restriction, working through an anti-oxidative mechanism. It appears an imbalance occurs in reduction-oxidation reactions (redox) during the aging process and that redox changes are minimized through the anti-oxidative action of calorie restriction (Cho 2003).

Additional information (also from the University of Texas Health Science Center) showed that animals chronically calorie restricted (as compared to those eating ad libitum) had limited oxidative stress as seen by rapid recovery in glutathione levels in previously ischemic (oxygen deprived) myocardium (heart muscle). The kappaB-responsive cytokines (interleukin-1beta and tumor necrosis factor-alpha) were transiently expressed in the calorie-restricted group but persisted longer in the group allowed to eat at will. In addition, expression of manganese superoxide dismutase, a key antioxidant enzyme, was delayed in the group receiving unlimited calories. Collectively these data indicate that calorie restriction significantly reduces myocardial oxidative stress and the postischemic inflammatory response (Chandrasekar et al. 2001; Sreekumar et al. 2002).

Calorie Restriction and Dementia

Researchers at Pukyong National University (Korea) evaluated the effect of dietary restriction on oxidative stress in the SAMP8 dementia mouse model. Female mice were allowed to eat ad libitum or fed about 60% of food allowed animals eating unrestricted diets. Results showed that basal metabolic rates were lowered by 15 to 22% and that the amounts of lipofuscin, a product of free radical damage, were reduced by 16% in dietary-restricted mice. At 4, 8, and 12 months of age, the superoxide radical was lowered approximately 45%. Grading score of senescence resulted in a marked improvement (about twofold among those dietary restricted).

Neurotransmitters (acetylcholine, dopamine, norepinephrine, and serotonin) were significantly increased in those following dietary restrictions. At 12 months of age, the generation of reactive oxygen species (ROS) in the brain decreased by 20% in the dietary restricted group compared with those eating ad libitum. Monoamine oxidase-B (MAO-B), an enzyme that increases oxidative deamination in the brain, was suppressed by 7 to ~10%. These results suggest that the inhibitory effect of oxidative stress by dietary restriction plays a pivotal role in reducing the age-related changes observed in dementia animal models (Choi et al. 2000; Kim et al. 2000). Comment: Monoamine oxidase is a source of H2O2 (hydrogen peroxide). Hydroxyl radicals, the most potent of all radicals, are produced from hydrogen peroxide and oxygen reactions, and gamma rays from low wavelength electromagnetic radiation. Such toxic reactions contribute significantly to the aging process and form the cornerstone of the free radical theory of aging.

Apart from inhibiting oxidative stress, researchers at the University of Florida (Gainesville) recently offered other explanations for the benefit of caloric restriction in protecting against age-related brain cell death. Researchers determined that certain proteins linked to cell death that naturally increase with age were reduced in the brains of rats whose calories were limited. More importantly, they found the levels of a beneficial protein known to provide potent protection against neuron death were twice as high in older rats whose calories were restricted by 40% (UF 2002). In addition, individuals with the APOE epsilon 4 gene (a gene associated with Alzheimer's disease), whose calorie consumption was the highest had 2.3 times the risk of developing Alzheimer's than did those with the gene who consumed the least calories (Luchsinger et al. 2002).

These findings have significant implications not only for alleviating the memory loss and other mental declines that accompany normal aging, but also for a host of disorders related to excessive loss of brain cells (approximately 4 million people in the United States are afflicted with Alzheimer's and Parkinson's diseases).

Calorie Restriction Benefits Diabetics

F344 rats on a CRON diet showed a 15% reduction in blood glucose, which could also mean less protein cross-linkage (glucose increases non-enzymatic glycosylation, a major contributor to aging and perhaps cancer, as well as the complications arising from diabetes). Reduction of blood levels of glycated hemoglobin has been observed in both human and animal studies when hyperglycemia (high blood glucose) was treated with a CRON diet. It is speculated that glycation of collagen in the kidney could be a factor in diabetic kidney failure, and that glycation of capillary membranes could contribute to age-related insulin resistance (Best 1995).

Researchers at the University of Wisconsin reached similar conclusions showing that rhesus monkeys (eating ad libitum for 6-8 hours per day) had higher basal glucose, basal insulin, and insulin responses to glucose, as well as decreased insulin sensitivity. Conversely, monkeys fed a dietary restricted diet (30% less than controls) showed decreases in the same glucose/insulin parameters and an increase in insulin sensitivity. Insulin changes were significantly related to changes in adiposity (weight and abdominal circumference) (Kemnitz et al. 1994).

Harvard researchers recently published an interesting perspective regarding enhanced longevity and calorie restriction. After studying genetically altered mice it was determined that a lean body (devoid of fat) may be more significant in determining life span than a calorie-restricted diet. The mice in the study were able to eat whatever they wanted and still stay slim because their fat tissue had been altered so it could not respond to the hormone insulin (insulin helps to move sugar from the blood into body cells and also helps fat cells to store fat). Although the altered mice ate 55% more food per gram of body weight than normal mice, they had 70% less body fat by the time they reached 3 months of age. Ultimately, the mice were protected against obesity.

Interestingly, both male and female mice increased mean life span (approximately 134 days or 18%), with parallel increases in median and maximum life spans. Thus, a reduction of fat mass (even without caloric restriction) appears assocated with increased longevity in mice, possibly through effects on insulin signaling.

These findings could open the possibility of a new drug that would fight obesity, and related illnesses like Type-2 diabetes, by blocking insulin receptors in fat tissue. However, the drug would need to be targeted to fat only because a loss of insulin sensitivity throughout the body results in Type-2 diabetes (Bluher et al. 2003; Mercola 2003b).

Comment: The dangers of hyperinsulinemia (excesses of insulin in the bloodstream) are now beyond debate (many forms of degenerative disease manifest with the appearance of insulin excesses).

How the Immune System Responds to Calorie Restriction

Researchers at Tufts University showed that a moderate caloric restriction in humans appears to have a beneficial effect on cell-mediated immunity (Santos et al. 2003). Cell-mediated immune reactions defend against certain bacterial, fungal, and viral pathogens, as well as malignant cells and other foreign protein or tissue. Allergic dermatitis is an example of a cell-mediated immune response.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are generally increased in the sera of aged humans and mice; the dysregulation of these cytokines is frequently observed in immune dysfunction. Current studies show that older mice subjected to long-term calorie restriction had serum levels of TNF and IL-6 comparable to those of young mice (Spaulding et al. 1997; Kim 2002). Comment: Production of TNF-a can activate nuclear factor-kappaB (NF-kB), a transcription factor. Once activated, NF-kB becomes a potent stimulus to cytokine production. Excesses of IL-6, a pro-inflammatory cytokine, have been demonstrated in immune irregularities, heart disease, arthritis, and cancer.

Calorie Restriction and Malignancies

In 1909, Moreschi observed that tumors transplanted into underfed mice did not grow as well as those transplanted into mice fed ad libitum. This finding stimulated a decade of research, which showed that caloric restriction also affected the growth of spontaneous tumors. Between 1920 and 1940 little work was done in this area, possibly because of limited methodology, but in the 1940s the laboratories of Tannenbaum (Chicago) and Baumann (Wisconsin) were able to design studies using defined diets. The researchers showed that the positive effects of calorie restriction were due to the caloric content of the diet independent of the source of the calories.

After another decade, research in the calorie-cancer area declined until it was reborn in the 1980s. By this time, knowledge of physiology and molecular biology had advanced enough to allow investigators to probe mechanisms underlying the calorie-cancer phenomenon. It was determined that energy restriction (fewer calories) enhances DNA repair, moderates oxidative damage to DNA, and reduces oncogene expression, a potentially cancer-causing gene; less caloric intake also favorably influences insulin metabolism. These observations explain some of the basic mechanisms involved in over-consumption and the establishment and proliferation of tumors (Moreschi 1909, 1914; Kritchevsky 1995, 2001).

In 1999, Japanese researchers assigned calorie restriction to both young adult and full adult mice to determine whether there was a delay in the onset of spontaneous hepatomas (malignant liver tumors) or a reduction in their frequency. Both groups showed striking reductions in spontaneous hepatomas, from 70.9 among mice eating ad libitum down to 35.7 (calorie restriction begun in the young adult stage) and 30.4 (calorie restriction begun in the full adult stage). The numbers of tumor-free mice in the restricted groups increased by 45.7% and 38.5%, respectively, from 11.5% in the non-restricted control group. When the cumulative incidences of small hepatomas were compared between the two restricted groups, restriction started at the young adult stage allowed fewer initiation stresses and delayed promotion of the tumors (Yoshida et al. 1999).

Researchers from Boston College recently reported that even moderate dietary restriction appeared an effective antiangiogenic therapy on recurrent malignant brain cancers (CT-2A syngeneic malignant mouse astrocytoma cells underwent a 80% inhibition following calorie restriction). Dietary restriction appears to shift the tumor microenvironment from a proangiogenic (favoring a well developed vascular system to nurture the growing tumor) to an antiangiogenic state (void of a healthy vasculature) through multiple effects on the tumor cells and the tumor-associated host cells (Mukherjee et al. 2002).

Calorie restriction is also pro-apoptotic, meaning it promotes the suicide of damaged cells. In order to maintain health, damaged cells have to make a decision as to whether they are going to undergo repair and if they elect restoration, the cell has to decide if the repair was successful. If the cellular damage was too extreme (with the cell exhibiting signs of cancerous possibilities) the cell needs to make the decision to commit suicide. Chaperones (stress proteins that help polypeptides assume their proper shape) participate in the decision concerning whether a cell will destroy itself by increasing the secretion of proteins that inhibit apoptosis. Thus, high chaperone levels (as occurs with age) tend to make abnormal cells less apt to commit suicide. Calorie restriction lowers chaperone levels so that the decision to commit cellular suicide in damaged and pre-cancerous cells is more likely to occur. Comment: In every tissue, a balance must be struck between the need to maintain cell numbers and function, and the need to eliminate damaged, potentially toxic cells. For example, in non-dividing cells, such as neurons, calorie restriction appears to induce chaperone expression, which enhances cell survival and may delay the onset of neurologic disorders of aging, including Alzheimer's disease, Parkinson's disease and stroke. Conversely, in dividing cells (such as liver cells) calorie restriction reduces chaperones, encouraging the death of abhorrent, precancerous cells (Wickner et al. 1999; Spindler 2001a; Suh et al. 2002; Kent 2003).

Although the anti-cancer effects of calorie restriction are well established, Dr. Stephen R. Spindler (Head of Technology at BioMarker Pharmaceuticals) does not recommend calorie restriction for individuals with cancer. According to Dr. Spindler, "There is no question that under-eating improves our health, but I don't think that we should take sick people and try to improve their health by under-feeding them."

The Effects of Calorie Restriction on p53, IGF-1, and Leptin

Heterozygous p53-deficient mice are prone to spontaneous neoplasms, most commonly sarcoma and lymphoma; the median time to death is 18 months. It was previously shown that juvenile mice (eating 60% of an ad libitum diet) delayed tumor development by a p53-independent and insulin-like growth factor-1 (IGF-1)-related mechanism.

To determine whether calorie restriction is equally effective when started in adult p53-deficient mice and to compare chronic calorie restriction with an intermittent fasting regimen, male mice (7-10 months old), were randomly assigned to the following feeding schedules: (1) mice were allowed to eat ad libitum, (2) mice were calorie restricted to 60% of ad libitum intake, or (3) mice were fasted 1 day per week (food availability on non-fasting days was controlled to prevent overeating). The researchers concluded that calorie restriction or a 1 day-per week fast suppressed carcinogenesis, even when started late in life in mice predestined to develop tumors due to a deficient p53 gene (Poetschke et al. 2000; Berrigan et al. 2002).

In a separate group of p53 deficient mice, plasma IGF-1 levels in calorie-restricted mice versus mice allowed to eat ad libitum were reduced by 20% after 4 weeks treatment. Leptin levels in the calorie-restricted mice were also reduced by 71%, while those fasted had intermediate levels of leptin and IGF-1 (Berrigan et al. 2002).

Explanatory Comments
  • p-53
  • Insulin-like Growth Factor-1 (IGF-1)
  • Leptin
The following comments explain how caloric restriction (acting upon p53, IGF-1, and leptin) could significantly influence life span.


Often called the guardian of the genome, p53 prevents replication of damaged DNA in normal cells and promotes suicide or apoptosis of cells with abnormal DNA. Faulty p53 molecules allow cells (carrying damaged DNA) to survive when they would normally die and to replicate when they would normally stop. Thus, a lack of p53 regulation promotes the spontaneous emergence of mutant cells, a cellular distortion invitational to cancer (Greenblatt et al. 1994; Oliff et al. 1996).

Nonetheless, most of nature appears to work best when in balance, not showing hyper (over) or hypo (under) responsiveness. Scientists recently found that mice with high activity of the tumor-suppressing p53 gene had low rates of cancer, but aged prematurely. The finding suggests that aging might occur, in part, because of the body's innate vigilance against cancer. Researchers at Baylor College of Medicine (Houston, Texas) generated mutant mice with revved up p53. As expected, the mice were more resistant to cancer than normal mice, but despite this protection the mutant mice had (roughly) a 20% shorter life span. Instead of cancer, the animals experienced bone thinning, organ breakdown, vulnerability to physical stress, and the equivalent of sagging skin, and balding in humans. Researchers speculate that hyperactivity in the p53 gene may disable the body's reserve of stem cells sooner than normal. This would keep primitive cells from replenishing certain body tissues and lead to premature tissue degeneration (Ferbeyre et al. 2002; infoaging.org 2003).

Insulin-like Growth Factor-1 (IGF-1)

The journal Cancer Research reported in 1997 that a reduction in caloric intake dramatically slowed cancer progression in rodents, offering a prophylactic as well as a therapeutic advantage. Part of the rationale hinges on the fact that dietary restriction lowers IGF-1, a growth factor involved in cell proliferation, apoptosis (cell death), and tumorigenesis, by about 24%.

Researchers found that mice dosed with a carcinogen known to induce bladder cancer but consuming 20% fewer calories had far fewer tumors than mice on a normal caloric diet. It was determined that cancer's uncontrolled development and malignant properties appear to be stimulated by IGF-1 and that calorie restriction reduces this multifaceted growth factor. As IGF-1 levels were reduced, the stage and virulence of existing cancerous tumors were also reduced. Conversely, if IGF-1 levels were restored, the protective effect of caloric restriction disappeared and the stage of the cancer advanced. Rates of apoptosis were 10 times higher among dietary restricted mice compared to those eating ad libitum or dietary restricted mice undergoing IGF-1 restoration. Administering IGF-1 to dietary restricted mice increases cell proliferation 6-fold. Although the research involved bladder cancer, scientists believe that IGF-1 may modulate pivotal stages in cancer development generically (Dunn et al. 1997; Hansen 2002).


Researchers at the University of Texas M.D. Anderson Cancer Center suggest that measuring a woman's leptin levels could be another relevant indicator to detect her risk of developing breast cancer. The study (published in the Proceedings for the 2003 Annual Meeting of the American Association for Cancer Research) found that a woman's production of leptin might reveal her history of fat consumption.

Calculating leptin levels appears to offer more prognostic data than just measuring body mass index and the amount of fat the woman currently consumes (ANI 2003).

Apart from being a predictive indicator of breast cancer risk, Japanese researchers showed that hyperleptinemia (excesses of leptin in the bloodstream) increases breast cancer cell proliferation through accelerated cell cycle progression (Okumura et al. 2002).

Researchers also recently confirmed that leptin influences cellular differentiation (the departure of a cell from the appearance of a normal, healthy cell) and the progression of prostate cancer. Leptin appears to have a role in the development of prostate cancer through testosterone and factors related to obesity (Saglam et al. 2003).

The West of Scotland Coronary Prevention Study (WOSCOPS) showed that hyperleptinemia also has linkage with cardiovascular disease. For each 1 standard deviation (the variation in the value of a variable) increase in leptin, the relative risk of a cardiovascular event increased by 25%. The WOSCOPS was the first, large, prospective study to show that leptin is a novel, independent risk factor for coronary heart disease (Wallace et al. 2001).

Pakistani researchers recently reported that leptin levels are increased in obesity and that the hormone may play a role in the development of insulin resistance and non-insulin dependent diabetes mellitus (Haque et al. 2003).

Cotninued . . .

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