Marinac CR, Nelson SH, Breen CI, et al. Prolonged nightly fasting and breast cancer prognosis [published online ahead of print March 31, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2016.0164.
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
Design and Participants
Investigators collected and analyzed data from 2,413 women with breast cancer who participated in the Women’s Healthy Eating and Living (WHEL) study between March 1, 1995 and May 3, 2007. The women ranged in age from 27 to 70 years (mean age 52.5 years) at diagnosis. None of the participants had diabetes mellitus. Mean study follow-up was 7.3 years; breast cancer or any cause mortality was tracked for 11.4 years. Data analysis was conducted from May 18 to October 5, 2015.
Study Medication and Dosage
Duration of nightly fasting was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4 of the study.
Clinical outcomes were invasive breast cancer recurrence and new primary tumors during the 7.3 years of follow-up as well as death from breast cancer or any cause during the 11.4 years of surveillance. Baseline sleep duration was self-reported and archived blood samples were used to assess concentrations of hemoglobin A1c (HbA1c) and C-reactive protein (CRP). Body mass index (BMI) was calculated using data from body measurements collected during the study.
The women in this cohort fasted for a mean (SD) duration of 12.5 (1.7) hours per night. Fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with a 36% increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night [hazard ratio (HR): 1.36; 95% confidence interval (CI): 1.05-1.76] when analyzed through (repeated-measures) Cox proportional hazards regression models. Nightly fasting for less than 13 hours was associated with a nonsignificant trend toward higher risk of breast cancer mortality (HR: 1.21; 95% CI: 0.91-1.60) and all-cause mortality (HR: 1.22; 95% CI: 0.95-1.56).
This appears to be the first human study that has sought a direct association between nightly fasting and breast cancer outcome.
In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower HbA1c 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).
Based on their findings, the investigators concluded that simply extending the length of the nightly fasting period could be a medication-free strategy to reduce the risk of breast cancer recurrence. They surmised that the positive effects of nightly fasting on prognosis may be related to improved sleep and improved glucose regulation.
As practitioners of natural medicine, we always seek simple lifestyle changes that will improve health. In patients with a history of breast cancer, health improvement strategies are often focused on reducing the risk of recurrence. This study suggests an elegantly simple intervention that may have meaningful benefit: prolonging the period of time in which women abstain from food at night—the fasting period between dinner and breakfast. In this cohort of women for whom the mean fasting period was 12.5 hours, those who fasted fewer than 13 hours per night had a 36% higher risk of breast cancer recurrence.
This appears to be the first human study that has sought a direct association between nightly fasting and breast cancer outcome. In animals, caloric restriction is an effective way to reduce cancer risk.1 Interestingly, in animals, intermittent caloric restriction prevents breast cancer development as well as or even better than chronic caloric restriction.2 Only 1 study has examined whether meal timing has an effect on tumor progression in mice. Mice whose feeding times were restricted had smaller tumors than mice fed ad libitum.3 Curiously, feeding mice when it was light was also associated with less tumor growth.
In this group of women who were part of the well-known WHEL study cohort, longer nightly fasting was associated with a lower HbA1c level, a finding that was similar to what was reported in 2010 by Giovanucci et al, who analyzed data from the National Health and Nutrition Examination Survey (NHANES).4 It may be that longer fasting lowers both blood sugar and/or insulin production, 2 actions that may limit growth of breast cancer cells. Erickson et al reported in 2011 in a different analysis of data from the WHEL cohort that women with an HbA1c >7.0% had an HR for all-cause mortality of 2.35 (95% CI: 1.56-3.54) compared to women with an HbA1c less than 6.5%.5
In an August 2015 analysis of NHANES data, Marinac et al reported that among 2,019 women, longer nighttime fasting was associated with significantly lower CRP levels, but only in women who ate fewer than 30% of their daily calories after 5 pm.6
In this current paper, longer nightly fasting was not correlated with BMI. Longer fasting was associated with long sleep duration. Late-night eating disrupts circadian rhythms. Eva Schernhammer’s multiple studies of night-shift workers have produced convincing evidence that circadian misalignment is linked with increased cancer risk, including increased risk of breast cancer.7
While these findings are the result of retrospective analysis of data gathered 2 decades ago, the results are intriguing. There are those who will suggest we wait for more definitive data gathered from a prospective randomized trial before bringing this practice into clinical use. I am not among that group, because there is currently no evidence that longer nighttime fasting is associated with any increase in risk. At the worst it may prove ineffective. Because this study suggests a nearly 40% shift in cancer recurrence rates, longer nighttime fasts may have considerable value.
The obvious question that we do not and will not know the answer to is whether the association revealed by this data is causal or not. It could be that women who produce higher amounts of insulin choose to forgo long nighttime fasts because they become hypoglycemic easier. It may turn out that this eating pattern serves more as a biomarker than an intervention.
To our already simple prescriptions for daily exercise, a healthy Mediterranean diet, and adequate sleep, we should add this recommendation for our breast cancer patients: “Eat an early dinner and a late breakfast.” It sounds almost too simple.
- Pariza MW. Calorie restriction, ad libitum feeding, and cancer. Proc Soc Exp Biol Med. 1986;183(3):293-298.
- Rogozina OP, Nkhata KJ, Nagle EJ, Grande JP, Cleary MP. The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding. Breast Cancer Res Treat. 2013;138(2):395-406.
- Wu MW, Li XM, Xian LJ, Lévi F. Effects of meal timing on tumor progression in mice. Life Sci. 2004;75(10):1181-1193.
- Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33(7):1674-1685.
- Erickson K, Patterson RE, Flatt SW, et al. Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol. 2011;29(1):54-60.
- Marinac CR, Sears DD, Natarajan L, Gallo LC, Breen CI, Patterson RE. Frequency and circadian timing of eating may influence biomarkers of inflammation and insulin resistance associated with breast cancer risk. PLoS One. 2015;10(8):e0136240.
- Schernhammer ES, Laden F, Speizer FE, et al. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001;93(20):1563-1568.