Transient caloric restriction and cancer risk (The Netherlands) (original) (raw)
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Breast Cancer Risk After Caloric Restriction During the 1944-1945 Dutch Famine
JNCI Journal of the National Cancer Institute, 2004
Background: Data from animal models suggest that caloric restriction may reduce the risk of breast cancer, although not all dietary regimens produce similar effects. We examined whether caloric restriction imposed as a consequence of the 1944 -1945 Dutch famine reduced the risk of breast cancer in women participating in a Dutch breast cancer screening program. Methods: Between 1983 and 1986, approximately 15 000 women, aged 2 to 33 years during the 1944 -1945 Dutch famine, responded to a questionnaire about their famine experience. A famine exposure score, graded as absent, moderate, or severe exposure, was derived from answers regarding hunger, cold, and weight loss. During follow-up until January 2000, 585 women with incident breast cancer were identified by the regional cancer registry. The relationship between famine exposure and breast cancer risk was assessed by weighted Cox regression models, in which person-years lived for the entire cohort was extrapolated from data from a random sample of 15% of the cohort. Results: Women who were severely exposed to the famine had a statistically significantly higher risk of breast cancer (hazard ratio [HR] ؍ 1.48, 95% confidence interval [CI] ؍ 1.09 to 2.01) than women who were not exposed. Women who were moderately exposed to the famine had a 13% increased risk of breast cancer (HR ؍ 1.13, 95% CI ؍ 0.92 to 1.38; P trend ؍ 0.016). The association between famine exposure and breast cancer risk was stronger for women who were exposed between the ages of 2 and 9 years (severely exposed versus unexposed: HR ؍ 2.01, 95% CI ؍ 0.92 to 4.41) than for women who were exposed at older ages. Conclusions: The risk of breast cancer was increased in women who were severely exposed to a short but severe famine decades earlier. This result is compatible with data from the few animal studies investigating effects of shortterm, transient caloric restriction. [J Natl Cancer Inst 2004; 96:539 -46]
Scientific Reports, 2016
Both chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) have shown anticancer effects. However, the direct evidence comparing ICR to CCR with respect to cancer prevention is controversial and inconclusive. PubMed and Web of Science were searched on November 25, 2015. The relative risk (RR) [95% confidence interval (CI)] was calculated for tumor incidence, and the standardised mean difference (95% CI) was computed for levels of serum insulin-like growth factor-1 (IGF-1), leptin, and adiponectin using a random-effects meta-analysis. Sixteen studies were identified, including 11 using genetically engineered mouse models (908 animals with 38-76 weeks of follow-up) and 5 using chemically induced rat models (379 animals with 7-18 weeks of follow-up). Compared to CCR, ICR decreased tumor incidence in genetically engineered models (RR = 0.57; 95% CI: 0.37, 0.88) but increased the risk in chemically induced models (RR = 1.53, 95% CI: 1.13, 2.06). It appears that ICR decreases IGF-1 and leptin and increases adiponectin in genetically engineered models. Thus, the evidence suggests that ICR exerts greater anticancer effect in genetically engineered mouse models but weaker cancer prevention benefit in chemically induced rat models as compared to CCR. Further studies are warranted to confirm our findings and elucidate the mechanisms responsible for these effects. Cancer is, to some extent, a preventable disease that is presumably caused by a combination of genetic, environmental, and behavioural factors 1. Several reviews have discussed how diet and nutrition contribute to human cancer risk 2-6 by affecting the initiation, promotion and progression of cancers 7-9. Two main types of dietary restriction are chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) (e.g., intermittent fasting, alternate-day fasting, or routine periodic fasting) 10-13. Two population-based studies have found a linear and inverse association between CCR and breast cancer risk 14,15. However, because CCR requires constant food restriction, the tolerance and compliance for fasting is unsatisfactory; therefore, the effect of CCR might not be as good as expected. Researchers have been looking for more feasible styles of calorie restriction (CR) with comparable or even superior results. Currently, ICR regimens have been found to be equivalent to, if not better than, CCR for weight loss, providing an alternative approach for weight loss that might be better suited to some individuals 16. Several population studies have shown that ICR can improve indicators of chronic diseases (e.g., insulin sensitivity, high density lipoprotein cholesterol and fat oxidation) 17-19. The question of whether ICR show better tumor inhibitory effects than CCR remains unanswered. Unfortunately, most research focuses on animal models. There is little evidence from human studies.
The Journal of nutrition, 2004
Most studies on calorie deprivation and cancer risk in rodents show reductions in tumor occurrence. However, the few human studies on calorie restriction are conflicting. An overview is given of results in the DOM (diagnostic onderzoek mammacarcinoom) cohorts among women exposed to the Dutch Famine of 1944-1945. Opposing effects were found on risk factors (shortening of leg length, later menarche, and earlier menopause), whereas urinary estrogens and plasma insulin-like growth factor (IGF)-1 and IGF binding protein-3 were increased, as was breast cancer itself. Exposure between 2 and 10 y old was an unexpected window of susceptibility to the effects of calorie deprivation. The effects of famine exposure were most clearly seen in women who never gave birth. These opposing observations can be explained by a neurodevelopmental hypothesis on set-point shifts at the level of the diencephalons/hypothalamus, either directly or from rebound effects. Such a mechanism reflects old evolutionar...
Effect of caloric restriction on pre-malignant and malignant stages of mammary carcinogenesis
Carcinogenesis, 1997
CO 80214, USA chemical species (adrenal cortical steroid) that may be 1 To whom correspondence and reprint requests should be addressed involved in mediating the protective effects of energy Caloric restriction has documented beneficial effects on restriction. These data indicate the feasibility of identifying numerous diseases including cancer, yet the mechanism(s) a chemical basis for the protective effect of caloric restricthat accounts for these wide ranging benefits is unknown.
The 1944-1945 Dutch Famine and Subsequent Overall Cancer Incidence
Cancer Epidemiology Biomarkers & Prevention, 2005
Caloric restriction seems to be the most potent dietary intervention to protect against a variety of cancers in animals. We investigated whether overall cancer risk is affected in humans after exposure to a brief famine, followed by a period of abundance. We used data of f15,000 women who were exposed at various degrees to the 1944-1945 Dutch famine at ages between 2 and 33 years. Between 1983 and 1986, these women were asked about their individual experiences of famine exposure (, 1,602 new cancer cases were identified by the regional cancer registry. We assessed the relation between famine and total cancer risk by weighted Cox regression models, in which a 15% random sample was used to represent person-years lived in the entire cohort. In these models, we adjusted for potential confounders. Overall cancer risk was increased in women having been severely famine exposed compared with women having been unexposed (hazard ratio, 1.25; 95% confidence interval, 1.01-1.55). Exclusion of breast cancer cases from our analyses showed that this increase in risk was largely driven by the previously reported increase in breast cancer risk: women who were severely exposed to the famine were at a 1.12 (95% confidence interval, 0.87-1.43) times increased risk of non-breast cancer compared with the unexposed. In conclusion, we found no indications that this brief famine has affected overall cancer risk, exclusive of breast cancer. Counteracting increased caloric intake following the famine, however, may have obscured any relation. (Cancer Epidemiol Biomarkers Prev
Technology in cancer research & treatment, 2007
While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people ...
Lipids, 1986
The experiments reported are part of our effort to dissociate the tumor-enhancing effects of dietary fat and high caloric intake. Rats either were fed ad libitum diets containing 4% corn oil or their calories were restricted by 40% and their diets contained 13.1% corn oil. Incidence of 7,12-dimethylbenz(a)anthracene {DMBAHnduced mammary tumors was 80% in rats fed ad libitum and 20% in those fed the calorie-restricted diets. Incidence of 1,2-dimethylhydrazine (DMH)oinduced colon tumors was 100% in rats fed ad libitum and 53% in those whose caloric intake was restricted by 40%. The tumor yield {tumors per tumor-bearing rat) was significantly lower in rats on caloric restriction. In another series, rats were fed diets containing 5, 15 or 20% corn oil ad libitum or were fed calorie-restricted (by 25%} diets which provided 20 or 26.6% corn oil (therefore, the same absolute amount of fat was consumed in each of the pair-fed groups). Tumor incidence and tumor yield in the two calorie-restricted groups were similar to those seen in the rats fed 5% fat ad libitum; tumor burden {total g of tumor) was 45-65% lower in the calorie-restricted rats. The data suggest that caloric intake is a more stringent determinant of tumor growth than fat intake. 272-274 (1986).
Energy restriction and the prevention of breast cancer
Proceedings of the Nutrition Society, 2012
Energy restriction (ER) to control weight is a potential strategy for breast cancer prevention. The protective effects of habitual continuous energy restriction (CER) and weight loss on breast tumour formation have been conclusively demonstrated in animal studies over the past 100 years, and more recently in women using data from observational studies and bariatric surgery. Intermittent energy restriction (IER) and intermittent fasting (IF) are possible alternative preventative approaches which may be easier for individuals to undertake and possibly more effective than standard CER. Here, we summarise the available data on CER, IER and IF with special emphasis on their potential for breast cancer prevention. In animals, IER is superior or equivalent to CER with the exception of carcinogen-induced tumour models when initiated soon after carcinogen exposure. There are no human data on IER and breast cancer risk, but three studies demonstrated IER and CER to be equivalent for weight loss. IF regimens also reduce mammary tumour formation in animal models and also led to weight loss in human subjects, but have not been directly compared with CER. Animal and some human data suggest that both IER and IF may differ mechanistically compared with CER and may bring about greater reduction in hepatic and visceral fat stores, insulin-like growth factor 1 (IGF-1) levels and cell proliferation, and increased insulin sensitivity and adiponectin levels. Although IER and IF were first studied 65 years ago, we conclude that further studies are required to assess their values compared with CER.