Catherine R. Marinac

Objectively measured physical activity is related to cognitive function in older adults.

To explore the relationship between cognitive functioning and time spent at different intensities of physical activity (PA) in free‐living older adults.

Postdiagnosis C-Reactive Protein and Breast Cancer Survivorship: Findings from the WHEL Study

Background: Serum C-reactive protein (CRP) is a marker of acute inflammatory response and has been associated with health outcomes in some studies. Inflammation and immune response may have potential prognostic implications for breast cancer survivors. Methods: The Womens Healthy Eating and Living Study includes 2,919 early-stage breast cancer survivors with serum collected 2 years postdiagnosis and follow-up for clinical outcomes over approximately 7 years. CRP concentrations were measured using high-sensitivity electrochemiluminescence assay. Outcomes, including all-cause mortality, breast cancer–specific mortality, and additional breast cancer events were oncologist verified from medical records and death certificates. Cox proportional hazards models were conducted with adjustment for potential confounding factors to generate HRs and 95% confidence intervals (CI). Results: CRP concentrations in women diagnosed with breast cancer were associated with death due to any cause, death due to breast cancer, and additional breast cancer events, after adjustment for sociodemographic and cancer characteristics (lnCRP: P < 0.05 for all three outcomes). The HR for women with (vs. without) acute inflammation suggests a threshold effect on overall survival, rather than a dose–response relationship (≥10.0 mg/L vs. <1 mg/L: HR, 1.96; 95% CI, 1.22–3.13). Associations were similar for breast cancer–specific mortality (HR, 1.91; 95% CI, 1.13–3.23) and any additional breast cancer–related event (HR, 1.69; 95% CI, 1.17–2.43). Conclusions: Acute inflammation status (CRP ≥ 10 mg/L) may be an important independent biomarker for long-term survival in breast cancer survivors. Impact: Interventions to decrease circulating CRP concentrations in breast cancer survivors with acute inflammation may improve prognosis. Cancer Epidemiol Biomarkers Prev; 23(1); 189–99. ©2013 AACR.

Intermittent Fasting and Human Metabolic Health

Periods of voluntary abstinence from food and drink (i.e., intermittent fasting) has been practiced since earliest antiquity by peoples around the globe. Books on ethnology and religion describe a remarkable variety of fasting forms and practices.1 Renewed interest in fasting regimens is evidenced by a plethora of popular press publications and diet recommendations. For example, in 2013, Mosley and Spencer published a best-selling book titled “The Fast Diet,” which touts the benefits of restricting energy intake severely for two days a week while eating normally the rest of the week.2 Dozens of books promote various fasting dietary patterns and the web offers hundreds of fasting-related sites. However, scientific evidence for the health benefits of intermittent fasting in humans is often extrapolated from animal studies, based on observational data on religious fasting (particularly Ramadan), or derived from experimental studies with modest sample sizes. The overall objective of this paper is to provide an overview of intermittent fasting regimens (Table 1) and summarize the evidence on the health benefits of intermittent fasting with a focus on human intervention studies. Because much of the data on intermittent fasting is from research in animal models, we briefly summarize key rodent studies and reviews. Health outcomes of interest are changes in weight and metabolic parameters associated with type 2 diabetes, cardiovascular disease, and cancer. We also present an overview of the major mechanisms hypothesized to link fasting regimens with human health: (1) circadian biology, (2) the gastrointestinal microbiota, and (3) modifiable lifestyle behaviors such as diet, activity, and sleep. Finally, we present conclusions regarding the evidence-base for intermittent fasting as an intervention for improving human health and propose a research agenda. Table 1 Types of intermittent fasting regimens that are hypothesized to impact health outcomes This paper provides a uniquely broad synthesis of the scientific evidence linking intermittent fasting with human health and a framework for future research on this topic.

Prolonged Nightly Fasting and Breast Cancer Risk: Findings from NHANES (2009–2010)

Background: A novel line of research has emerged, suggesting that daily feeding–fasting schedules that are synchronized with sleep-wake cycles have metabolic implications that are highly relevant to breast cancer. We examined associations of nighttime fasting duration with biomarkers of breast cancer risk among women in the 2009–2010 U.S. National Health and Nutrition Examination Survey. Methods: Dietary, anthropometric, and HbA1c data were available for 2,212 women, and 2-hour postprandial glucose concentrations were available for 1,066 women. Nighttime fasting duration was calculated using 24-hour food records. Separate linear regression models examined associations of nighttime fasting with HbA1c and 2-hour glucose concentrations. Logistic regression modeled associations of nighttime fasting with elevated HbA1c (HbA1c ≥ 39 mmol/mol or 5.7%) and elevated 2-hour glucose (glucose ≥ 140 mg/dL). All models adjusted for age, education, race/ethnicity, body mass index, total kcal intake, evening kcal intake, and the number of eating episodes per day. Results: Each 3-hour increase in nighttime fasting (roughly 1 SD) was associated with a 4% lower 2-hour glucose measurement [β, 0.96; 95% confidence interval (CI), 0.93–1.00; P < 0.05], and a nonstatistically significant decrease in HbA1c. Logistic regression models indicate that each 3-hour increase in nighttime fasting duration was associated with roughly a 20% reduced odds of elevated HbA1c (OR, 0.81; 95% CI, 0.68–0.97; P < 0.05) and nonsignificantly reduced odds of elevated 2-hour glucose. Conclusions: A longer nighttime duration was significantly associated with improved glycemic regulation. Impact: Randomized trials are needed to confirm whether prolonged nighttime fasting could improve biomarkers of glucose control, thereby reducing breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(5); 783–9. ©2015 AACR.

Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk

Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009–2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations.

Prolonged Nightly Fasting and Breast Cancer Prognosis

IMPORTANCE Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes. OBJECTIVE To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep. DESIGN, SETTING, AND PARTICIPANTS Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Womens Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015. EXPOSURES Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4. MAIN OUTCOMES AND MEASURES Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein. RESULTS The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26). CONCLUSIONS AND RELEVANCE Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.

Lifestyle Factors Associated with Cognitive Functioning in Breast Cancer Survivors

Weight, physical activity, and sleep are modifiable lifestyle factors that impact cognitive functioning in noncancer populations but have yet to be examined in cancer survivors. The aim of the study was to assess the relationship of obesity, physical activity, and sleep, with cognitive functioning among breast cancer survivors.

Recruitment strategies, design, and participant characteristics in a trial of weight-loss and metformin in breast cancer survivors

Weight loss and metformin are hypothesized to improve breast cancer outcomes; however the joint impacts of these treatments have not been investigated. Reach for Health is a randomized trial using a 2 × 2 factorial design to investigate the effects of weight loss and metformin on biomarkers associated with breast cancer prognosis among overweight/obese postmenopausal breast cancer survivors. This paper describes the trial recruitment strategies, design, and baseline sample characteristics. Participants were randomized in equal numbers to (1) placebo, (2) metformin, (3) weight loss intervention and placebo, or (4) weight-loss intervention and metformin. The lifestyle intervention was a personalized, telephone-based program targeting a 7% weight-loss in the intervention arm. The metformin dose was 1500 mg/day. The duration of the intervention was 6 months. Main outcomes were biomarkers representing 3 metabolic systems putatively related to breast cancer mortality: glucoregulation, inflammation, and sex hormones. Between August 2011 and May 2015, we randomized 333 breast cancer survivors. Mass mailings from the California Cancer Registry were the most successful recruitment strategy with over 25,000 letters sent at a cost of

Comparison of Accelerometry Methods for Estimating Physical Activity

191 per randomized participant. At baseline, higher levels of obesity were significantly associated with worse sleep disturbance and impairment scores, lower levels of physical activity and higher levels of sedentary behavior, hypertension, hypercholesterolemia, and lower quality of life (p<0.05 for all). These results illustrate the health burden of obesity. Results of this trial will provide mechanistic data on biological pathways and circulating biomarkers associated with lifestyle and pharmacologic interventions to improve breast cancer prognosis.

Internet-based physical activity intervention for women with a family history of breast cancer.

Purpose This study aimed to compare physical activity estimates across different accelerometer wear locations, wear time protocols, and data processing techniques. Methods A convenience sample of middle-age to older women wore a GT3X+ accelerometer at the wrist and hip for 7 d. Physical activity estimates were calculated using three data processing techniques: single-axis cut points, raw vector magnitude thresholds, and machine learning algorithms applied to the raw data from the three axes. Daily estimates were compared for the 321 women using generalized estimating equations. Results A total of 1420 d were analyzed. Compliance rates for the hip versus wrist location only varied by 2.7%. All differences between techniques, wear locations, and wear time protocols were statistically different (P < 0.05). Mean minutes per day in physical activity varied from 22 to 67 depending on location and method. On the hip, the 1952-count cut point found at least 150 min·wk−1 of physical activity in 22% of participants, raw vector magnitude found 32%, and the machine-learned algorithm found 74% of participants with 150 min of walking/running per week. The wrist algorithms found 59% and 60% of participants with 150 min of physical activity per week using the raw vector magnitude and machine-learned techniques, respectively. When the wrist device was worn overnight, up to 4% more participants met guidelines. Conclusion Estimates varied by 52% across techniques and by as much as 41% across wear locations. Findings suggest that researchers should be cautious when comparing physical activity estimates from different studies. Efforts to standardize accelerometry-based estimates of physical activity are needed. A first step might be to report on multiple procedures until a consensus is achieved.