Energy restriction and the prevention of breast cancer (original) (raw)
Related papers
The Journal of Nutrition, 2004
Failure to prevent adult weight gain is associated with an elevated risk for breast cancer. In general, an increase in body weight is accounted for by excess energy intake relative to energy expenditure. Efforts to control weight gain usually involve either a reduction in energy intake via dietary energy restriction (DER), an increase in energy expenditure via physical activity (PA), or both. However, it is not clear whether preventing weight gain by DER, PA, or their combination has comparable effects on the risk for cancer. Results from preclinical models indicate that DER results in a highly reproducible and dose-dependent inhibition of experimentally induced breast cancer. PA also inhibits mammary carcinogenesis, but whether these effects depend on energy balance is not clear. Emerging evidence indicates that reduced levels of circulating insulin-like growth factor (IGF) 1 (IGF-1) and elevated levels of corticosterone may be involved in DER-mediated protection against cancer; however, conditions of PA reported to protect against cancer can actually increase circulating levels of IGF-1. Mechanistic studies have shown that DER inhibits cell proliferation, creates a proapoptotic environment, and reduces blood vessel density adjacent to premalignant and malignant mammary pathologies; comparable information is not available from preclinical studies of PA and carcinogenesis. Additional research is needed to investigate the equivalence of DER, PA, and their combination in breast cancer prevention under comparable conditions of energy balance. J. Nutr. 134: 3407S-3411S, 2004.
Obesity Reviews, 2006
Excess adiposity over the pre-and postmenopausal years is linked to risk of postmenopausal breast cancer. Weight loss could potentially reduce risk amongst those with excess weight via beneficial effects on the hormonal (decreased circulating levels of oestradiol, testosterone, insulin) and secretory profiles of adipocytes (decreased production of leptin, tumour necrosis factor-a , interleukin 6 and increased production of adiponectin). Only modest reductions in adipose tissue are achieved and sustained with current weight loss programmes, which makes strategies to mitigate the adverse metabolic effect of adiposity a priority for cancer prevention. The adverse hormonal and secretory effects of adipose tissue are influenced substantially by acute changes in energy balance prior to changes in adiposity. Human and animal studies have shown dietary energy restriction to bring about favourable changes in circulating levels of insulin, leptin, sex hormone binding globulin, insulin-like growth factor-1, oestradiol, testosterone, reactive oxygen species, and the production and secretion of locally acting adipokines and inflammatory cytokines, that is, increased adiponectin and decreased interleukin-6. Achieving and sustaining energy restriction remains a difficult challenge. Intermittent energy restriction is a potential strategy for promoting periods of energy restriction on a long-term basis. Animal and human data suggest that intermittent energy restriction may have cancer preventative effects beyond that of chronic energy restriction and weight loss. Intermittent energy restriction may be a potential strategy for the primary prevention of breast cancer.
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.
Breast Cancer Research and Treatment, 2013
Previously we reported that intermittent calorie restriction (ICR) provided greater prevention of mammary tumors (MTs) than chronic calorie restriction (CCR). Here the impact of increased fat intake during refeeding in an ICR protocol was evaluated. MMTV-TGF-a female mice were assigned to one of three groups: ad libitum (AL) fed (n = 45) with free access to a moderately high fat diet (22 % fat calories); ICR (n = 45) 50 % calorie restricted for 3-week intervals followed by 3 weeks of 100 % of AL intake; and CCR (n = 45) fed 75 % of AL mice, matching each 6-week cycle of ICR mice. ICR mice were further designated as ICR-Restricted or ICR-Refed for data obtained during these intervals. All mice consumed the same absolute amount of dietary fat. Mice were followed to assess MT incidence, body weight and serum IGF-1, IGFBP3, leptin and adiponectin levels until 79 (end of final 3-week restriction) or 82 (end of final 3-weeks refeeding) weeks of age. Age of MT detection was significantly extended for CCR (74 weeks) and ICR (82 weeks) mice, compared to 57.5 weeks for AL mice. MT incidence for AL, ICR and CCR mice was 66.7, 4.4, and 52.3 %, respectively. Mammary and fat pad weights were reduced significantly following 50 % calorie restriction in ICR-Restricted mice compared to AL, CCR and ICR-Refed mice. IGF-1 and leptin levels also tended to be reduced in ICR-Restricted mice over the course of the study while adiponectin was not compared to AL, CCR, and ICR-Refed mice. The adiponectin:leptin ratio was consistently higher following 50 % restriction in ICR-Restricted mice. There was no relationship of IGF-1, leptin, or adiponectin with the presence of MTs in any groups. Thus the manner in which calories are restricted impacts the protective effect of calorie restriction independently of high fat intake.
Biomarkers of dietary energy restriction in women at increased risk of breast cancer
Cancer Prevention …, 2009
Dietary energy restriction (DER) reduces risk of spontaneous mammary cancer in rodents. In humans, DER in premenopausal years seems to reduce risk of postmenopausal breast cancer. Markers of DER are required to develop acceptable DER regimens for breast cancer prevention. We therefore examined markers of DER in the breast, adipose tissue, and serum.
Carcinogenesis, 2002
Because of the suggested role of energy consumption and the well-documented role of estrogens in the etiology of breast cancer, we have examined the effect of a 40% restriction of dietary energy consumption on the ability of administered 17β-estradiol (E2) to induce mammary tumorigenesis in female ACI rats. Experiments herein test the hypothesis that at least part of the inhibitory effect of energy restriction on mammary tumorigenesis is exerted downstream of potential effects of dietary manipulation on the production of estrogens by the ovaries. Ovary-intact ACI rats were fed a control or a 40% energy-restricted diet and were either treated continuously with E2 from subcutaneous Silastic tubing implants or received no hormone treatment. Mammary cancers rapidly developed in E2-treated rats fed the control diet; within 216 days of initiation of E2 treatment 100% of the population at risk exhibited palpable mammary tumors. Dietary energy restriction markedly inhibited E2-induced mammary tumorigenesis, as evidenced by significant reductions in cancer incidence and tumor burden as well as a significant increase in the latency to the appearance of the first palpable cancer. The inhibitory actions of dietary energy restriction on E2-induced mammary tumorigenesis were associated with an inhibition of E2-stimulated mammary cell proliferation. However, this inhibition was insufficient to block induction of lobuloalveolar hyperplasia or appearance of focal regions of atypical epithelial hyperplasia. These data suggest that dietary energy restriction inhibits E2-induced mammary cancer by attenuating or retarding the progression of atypical hyperplasia to carcinoma. Expression of progesterone receptor (PR) was up-regulated within the focal regions of atypical hyperplasia and the carcinomas induced by E2, regardless of whether the rats were fed the control or energy-restricted diet. However, circulating progesterone was reduced by dietary energy restriction, suggesting a possible mechanism for inhibition of mammary tumorigenesis. Dietary energy restriction did not inhibit the ability of administered E2 to induce prolactin (PRL)-producing pituitary tumors and associated hyperprolactinemia, indicating that the inhibitory effects of dietary energy restriction on mammary
Experimental biology and medicine (Maywood, N.J.), 2007
Chronic caloric restriction (CCR) prevents mammary tumorigenesis in rodents, but a protective effect for intermittent caloric restriction (ICR) is less well documented. We recently reported that ICR reduced mammary tumor (MT) incidence of mouse mammary tumor virus-transforming growth factor (MMTV-TGF)-alpha mice to a greater extent than did CCR. Here, we repeated this protocol and obtained serum and tissue samples. Ad libitum (AL) MMTV-TGF-alpha mice were fed AIN-93M diet. Beginning at 10 weeks of age, ICR mice received isocaloric AIN-93M-mod diet (2-fold increases in protein, fat, vitamins, and minerals) at 50% of ad libitum for 3 weeks followed by 3 weeks refeeding with AIN-93M diet. CCR mice were pair-fed AIN-93M:AIN-93M-mod (2:1) matching intakes for restriction/refeeding cycles. Mice were sacrificed for MT size, at 79 (end of 12th restriction) or at 80 (1 week after 12th refeeding) weeks of age. AL and ICR-80 mice had heavier body weights than ICR-79 and CCR mice (P < 0.0001...
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.