Abstract Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to ...metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16–48 h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease Parkinson’s disease and stroke. Studies of IF (e.g., 60% energy restriction on 2 days per week or every other day), PF (e.g., a 5 day diet providing 750–1100 kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8 h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.
Summary
Significant weight gain occurs in women during young adulthood, which increases risk of diseases such as diabetes, cardiovascular disease, and many cancers. This review aims to inform future ...individually targeted weight gain prevention programmes and summarizes possible targets: key life events, mediators that influence energy intake and physical activity levels, and moderators that could identify groups of women at greatest risk. Life events affecting weight include pregnancy and motherhood, smoking cessation, marriage and cohabiting, attending university, and possibly bereavement. Research has identified successful methods for preventing weight gain associated with pregnancy and motherhood, which could now be used in practice, but evidence is inconclusive for preventing weight gain around other life events. Weight gain is mediated by lack of knowledge and skills around food and nutrition, depression, anxiety, stress, satiety, neural responses, and possibly sleep patterns and premenstrual cravings. A paucity of research exists into altering these to limit weight gain. Moderators include socioeconomic status, genetics, personality traits, and eating styles. More research is required to identify at‐risk females and engage them in weight gain prevention. There is a need to address evidence gaps highlighted and implement what is currently known to develop effective strategies to limit weight gain in young women.
Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of ...marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month) studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.
The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in ...refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model).
Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index. Tyrer-Cuzick and Gail 10-year risks were based on a questionnaire completed contemporaneously. Breast cancers were identified at the entry screen or shortly thereafter. The contribution of density to risk models was assessed using odds ratios (ORs) with profile likelihood confidence intervals (CIs) and area under the receiver operating characteristic curve (AUC). The calibration of predicted ORs was estimated as a percentage (observed vs expected (O/E) from logistic regression.
The analysis included 50,628 women aged 47-73 years who were recruited between October 2009 and September 2013. Of these, 697 had breast cancer diagnosed after enrolment. Median follow-up was 3.2 years. Breast density interquartile range odds ratio (IQR-OR) 1.48, 95 % CI 1.34-1.63, AUC 0.59 was a slightly stronger univariate risk factor than the Tyrer-Cuzick model IQR-OR 1.36 (95 % CI 1.25-1.48), O/E 60 % (95 % CI 44-74), AUC 0.57 or the Gail model IQR-OR 1.22 (95 % CI 1.12-1.33), O/E 46 % (95 % CI 26-65 %), AUC 0.55. It continued to add information after allowing for Tyrer-Cuzick IQR-OR 1.47 (95 % CI 1.33-1.62), combined AUC 0.61 or Gail IQR-OR 1.45 (95 % CI 1.32-1.60), combined AUC 0.59.
Breast density may be usefully combined with the Tyrer-Cuzick model or the Gail model.
Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is ...increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects.
Meal frequency and timing in health and disease Mattson, Mark P.; Allison, David B.; Fontana, Luigi ...
Proceedings of the National Academy of Sciences - PNAS,
11/2014, Volume:
111, Issue:
47
Journal Article
Peer reviewed
Open access
Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian ...timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.
Breast cancer is an increasing public health problem. Substantial advances have been made in the treatment of breast cancer, but the introduction of methods to predict women at elevated risk and ...prevent the disease has been less successful. Here, we summarize recent data on newer approaches to risk prediction, available approaches to prevention, how new approaches may be made, and the difficult problem of using what we already know to prevent breast cancer in populations. During 2012, the Breast Cancer Campaign facilitated a series of workshops, each covering a specialty area of breast cancer to identify gaps in our knowledge. The risk-and-prevention panel involved in this exercise was asked to expand and update its report and review recent relevant peer-reviewed literature. The enlarged position paper presented here highlights the key gaps in risk-and-prevention research that were identified, together with recommendations for action. The panel estimated from the relevant literature that potentially 50% of breast cancer could be prevented in the subgroup of women at high and moderate risk of breast cancer by using current chemoprevention (tamoxifen, raloxifene, exemestane, and anastrozole) and that, in all women, lifestyle measures, including weight control, exercise, and moderating alcohol intake, could reduce breast cancer risk by about 30%. Risk may be estimated by standard models potentially with the addition of, for example, mammographic density and appropriate single-nucleotide polymorphisms. This review expands on four areas: (a) the prediction of breast cancer risk, (b) the evidence for the effectiveness of preventive therapy and lifestyle approaches to prevention, (c) how understanding the biology of the breast may lead to new targets for prevention, and (d) a summary of published guidelines for preventive approaches and measures required for their implementation. We hope that efforts to fill these and other gaps will lead to considerable advances in our efforts to predict risk and prevent breast cancer over the next 10 years.
Intermittent energy restriction combined with a Mediterranean diet (IER+MED) has shown promise to reduce body fat and insulin resistance. In the Multiethnic Cohort Adiposity Phenotype Study, Japanese ...Americans had the highest visceral adipose tissue (VAT) when adjusting for total adiposity. We conducted this pilot study to demonstrate feasibility and explore efficacy of following IER+MED for 12 weeks to reduce VAT among East Asians in Hawaii. Sixty volunteers (aged 35-55, BMI 25-40 kg/m
, VAT ≥ 90 cm
for men and ≥ 80 cm
for women) were randomized to IER+MED (two consecutive days with 70% energy restriction and 5 days euenergetic MED) or an active comparator (euenergetic Dietary Approaches to Stop Hypertension (DASH) diet). Participants and clinic staff (except dietitians) were blinded to group assignments. IER+MED had significantly larger reductions in DXA-measured VAT and total fat mass (-22.6 ± 3.6 cm
and -3.3 ± 0.4 kg, respectively) vs. DASH (-10.7 ± 3.5 cm
and -1.6 ± 0.4 kg) (
= 0.02 and
= 0.005). However, after adjusting for total fat mass, change in VAT was not statistically different between groups; whereas, improvement in alanine transaminase remained significantly greater for IER+MED vs. DASH (-16.2 ± 3.8 U/L vs. -4.0 ± 3.6 U/L, respectively,
= 0.02). Attrition rate was 10%, and participants adhered well to study prescriptions with no reported major adverse effect. Results demonstrate IER+MED is acceptable, lowers visceral and total adiposity among East Asian Americans, and may improve liver function more effectively than a healthful diet pattern. ClinicalTrials.gov Identifier: NCT03639350.
There are widespread moves to develop risk-stratified approaches to population-based breast screening. The public needs to favour receiving breast cancer risk information, which ideally should ...produce no detrimental effects. This study investigates risk perception, the proportion wishing to know their 10-year risk and whether subsequent screening attendance is affected.
Fifty thousand women attending the NHS Breast Screening Programme completed a risk assessment questionnaire. Ten-year breast cancer risks were estimated using a validated algorithm (Tyrer-Cuzick) adjusted for visually assessed mammographic density. Women at high risk (⩾8%) and low risk (<1%) were invited for face-to-face or telephone risk feedback and counselling.
Of those invited to receive risk feedback, more high-risk women, 500 out of 673 (74.3%), opted to receive a consultation than low-risk women, 106 out of 193 (54.9%) (P<0.001). Women at high risk were significantly more likely to perceive their risk as high (P<0.001) and to attend their subsequent mammogram (94.4%) compared with low-risk women (84.2%; P=0.04) and all attendees (84.3%; ⩽0.0001).
Population-based assessment of breast cancer risk is feasible. The majority of women wished to receive risk information. Perception of general population breast cancer risk is poor. There were no apparent adverse effects on screening attendance for high-risk women whose subsequent screening attendance was increased.
We tested the hypothesis that body mass index (BMI) aged 20 years modifies the association of adult weight gain and breast cancer risk.
We recruited women (aged 47-73 years) into the PROCAS ...(Predicting Risk Of Cancer At Screening; Manchester, UK: 2009-2013) Study. In 47,042 women, we determined BMI at baseline and (by recall) at age 20 years, and derived weight changes. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for new breast cancer using Cox models and explored relationships between BMI aged 20 years, subsequent weight changes and breast cancer risk.
With median follow-up of 5.6 years, 1142 breast cancers (post-menopausal at entry: 829) occurred. Among post-menopausal women at entry, BMI aged 20 years was inversely associated HR per SD: 0.87 (95% CI: 0.79-0.95), while absolute weight gain was associated with breast cancer HR per SD:1.23 (95% CI: 1.14-1.32). For post-menopausal women who had a recall BMI aged 20 years <23.4 kg/m
(75th percentile), absolute weight gain was associated with breast cancer HR per SD: 1.31 (95% CIs: 1.21-1.42), but there were no associations for women with a recall BMI aged 20 years of >23.4 kg/m
(P
values <0.05).
Adult weight gain increased post-menopausal breast cancer risk only among women who were <23.4 kg/m
aged 20 years.
PDF
