Later Circadian Timing of Food Intake Is Associated with Increased Body Fat

Weight gain and obesity have been described as an epidemic and a complex problem in the United States. Previous research has linked poor diet to weight gain and high body fat, and eating later in the day has also been described as a risk factor for weight gain; however, the impact of an individual’s body clock, independent of the time of day of food consumption, has not been explored.

In a recent study published online in The American Journal of Clinical Nutrition (AJCN), BWH investigators examined the relationships between body fat and body mass index, in addition to the timing of food consumption, to time of day and to the body’s circadian or body clock. This is the first time that the timing of meals has been studied in real world settings, in relation to melatonin onset, which marks the onset of sleep.

“We found that the timing of food intake relative to melatonin onset, a marker of a person’s biological night, is associated with higher percent body fat and BMI, and not associated with the time of day, amount or composition of food intake,” stated lead author Andrew W. McHill, PhD, researcher with the Division of Sleep and Circadian Disorders at BWH. “These findings suggest that the timing of when you consume calories, relative to your own biological timing may be more important for health than the actual time of day.”

Researchers analyzed data collected from 110 college-age participants enrolled in a 30-day observational study to document sleep times and daily meal intake.  A mobile phone app was used to time-stamp, document and record the participants’ food intake over seven consecutive days of their regular routines. For one night during the 30-day study, participants were studied at the BWH Center for Clinical Investigation to assess the timing of their melatonin onset, marking onset of sleep, and their body composition.

Researchers found that individuals with high body fat percentages consumed most of their calories shortly before going to sleep when melatonin levels were high, compared to individuals with lower percentages of body fat. Researchers note that they were unable to detect a relationship between the clock hour of food intake, caloric amount, meal composition, activity/exercise level, or sleep duration, and either of these body composition measures.  The researchers acknowledged several limitations that need to be considered for future work, including the fact that the population of college-aged individuals may not be representative of the entire population in terms of food choice and circadian or body clock rhythm.

Researchers concluded that these results provide evidence that the consumption of food during the circadian evening/night, independent of more traditional risk factors such as amount or content of food intake and activity level, plays an important role in body composition.

The project was funded by the NIH and NSBRI and these are the grant numbers: NIH F32DK107146, T32HL007901, K24HL105664, R01HL114088, R01GM105018, 01HL128538, P01AG009975, R21HD086392, R00HL119618, R01DK099512, R01DK105072 and R01HL118601 and NSBRI HFP02802, HFP04201, HDP0006.

Paper cited: McHill, Andrew W et al. “Later circadian timing of food intake is associated with increased body fat” The American Journal of Clinical Nutrition DOI: 10.3945/ajcn.117.161588.

Drugs Targeting the Beta2-Adrenoreceptor Linked to Parkinson’s Disease

Lewy bodies – abnormal clumps of alpha-synuclein protein that accumulate in the brain – are a hallmark of Parkinson’s disease (PD). Traditional drug development approaches for PD have focused on clearing alpha-synuclein from the brain or on preventing its downstream effects. But researchers from Brigham and Women’s Hospital want to prevent alpha-synuclein from accumulating in the first place. To do so, the team searched for drugs that turn down alpha-synuclein production. They then tested the drugs in mice and stem cells and studied the health records of millions of people living in Norway. The results of their efforts, which point to a new drug development path for PD, are published in Science.

“Our study suggests a potential new pathway to target PD,” said corresponding author Clemens Scherzer, MD, a neurologist and principal investigator at the Ann Romney Center for Neurologic Diseases at BWH and Harvard Medical School.

The research team screened more 1,100 drugs already approved for treating diseases other than PD, looking for compounds that could be repurposed for lowering alpha-synuclein production in neuronal cells. They narrowed in on promising candidates: members of a class of drugs known as beta2-adrenergic agonists.

The team studied the effects of this class of drugs in mice, finding that it could significantly reduce alpha-synuclein levels. Working with collaborators from the University of Bergen, the team combed through data from the health records of more than 4 million Norwegians, pulling out information on patients who had been taking salbutamol, a beta2-adrenergic agonist commonly used to treat of asthma. They found that these patients were significantly less likely to develop PD – PD risk was reduced by 34 percent for those taking the drug compared to those who were not.

Conversely, people taking propranolol – a hypertension drug that increased alpha-synuclein production in cultured cells – were at greater risk for developing PD.

“Clinical trials will be needed to determine if these insights can be translated into patients with PD.” said Scherzer. “We are excited about this innovative drug development strategy. We hope it will speed up drug development for patients with PD and inspire therapeutic strategies for other brain diseases.”

Funding was provided by the Michael J. Fox Foundation; the National Institute of Neurological Disorders and Stroke; the U.S. Department of Defense; the M.E.M.O. Hoffman Foundation; Prinses Beatrix Spier Fonds; the American Parkinson’s Disease Association; the Parkinson’s Disease Foundation; the Branfman Family Foundation; the Canadian Institute of Health Research (to D.S.P.), Brain Canada through the Canada Brain Research Fund (with financial support from Health Canada), the Krembil Foundation; and the Heart and Stroke Foundation of Canada.

Paper cited: Mittal S et al. “b2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease” Science DOI: 10.1126/science.aaf3934

Population Health Impact of Infants Born Small for Gestational Age in Low-and Middle-Income Countries 

In low-and middle-income countries, it is common for babies to be born of low birth weight, due to either inadequate growth in utero (fetal growth restriction) and/or preterm birth, (birth before 37 weeks gestation). Maternal undernutrition, infections, poor access to health care and environmental exposures during pregnancy are risk factors for both of these conditions. Babies born too small or too soon are at a high risk of mortality, stunted growth, developmental delay, and chronic disease.

In results published online in BMJ on August 17, researchers at Brigham and Women’s Hospital and the Child Health Epidemiology Reference Group (CHERG), a global collaboration of over 40 investigators, used the first international, multiethnic birth weight standard, known as the INTERGROWTH-21st, to describe the global burden of suboptimal fetal growth, also referred to as “small for gestational age.” The researchers estimated that in 2012, 23.3 million infants, or almost 20 percent of live births, were born small for gestational age in low and middle income countries. Among these, 1.5 million babies were both premature and small for gestational age, and at substantially higher risk for adverse outcomes. They also estimated that 606,500 newborn deaths, or 22 percent, were attributable to being small for gestational age. The highest burden was in South Asia, where one in three infants is born small for gestational age and 26 percent of newborn deaths are attributable to being small for gestational age.

“By reducing the percentage of babies born small for gestational age to 10 percent in low and middle income countries (a level that we would expect in a multi-ethnic population of optimal pregnancy nutrition and health), we could prevent approximately 250,000 newborn deaths annually,” said lead author, Anne CC Lee, MD, MPH, pediatrician in the Department of Pediatric Newborn Medicine at BWH. “The prevention of fetal growth restriction is complex and requires better understanding of the causes within different populations. However, several feasible and evidence based interventions can be provided, even now, in low-resource settings, to improve the survival and outcomes of these vulnerable infants, including continuous skin to skin contact for very low birth weight babies, breast feeding support for parents, management of newborn infections and newborn resuscitation.”

According to Lee, implementing these proven interventions are key priorities to reduce newborn mortality in low and middle income countries.

This study was supported by the Bill and Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

Paper cited: Lee Anne CC, et al for the CHERG Small-for-Gestational Age-Preterm Birth Working Group “Estimates of burden and consequences of infants born small for gestational age in low and middle income countries with INTERGROWTH-21st standard: analysis of CHERG datasets” BMJ DOI: 10.1136/bmj.j3677

A New Opportunity for Palliative Care

Palliative care is a multidisciplinary approach aimed at improving the comfort and quality of life of patients with serious illnesses. While typically studied and utilized in diseases like end-stage cancer, a recently completed randomized, controlled clinical trial is the first to look at how palliative care can help patients with advanced stage heart failure. This study was published in JACC earlier this month.

“Heart failure (HF) is both physically and psychologically stressful. Patients with HF often experience depression, anxiety, physical discomfort and spiritual distress, all of which indicate that palliative treatment may be a source of relief as this disease advances,” said James A. Tulsky, MD, chief of the BWH Division of Palliative Medicine and co-principal investigator of this study.

The study, conducted at Duke University Hospital (where Tulsky was formerly Chief of Palliative Care), enrolled 150 patients with advanced HF and randomly assigned half of them to receive standard care, while the other half received standard care plus a palliative care intervention. Standard care patients received treatment exclusively from a cardiology team. The other half were additionally treated by a palliative nurse and physician who addressed symptoms, conducted advance care planning, treated emotional suffering, and responded to spiritual concerns of the HF patients. After six months all of the patients in the study answered questionnaires that analyzed their quality of life, comfort and mental health.

Tulsky and his team found improved physical and spiritual quality of life as well as decreased depression and anxiety in the patients who received palliative care as part of their treatment. There was no difference in re-hospitalization or mortality rates between the two groups.

“Treating patients with end-stage HF is not just about prolonging life; it’s also about improving the quality of life,” said Tulsky. “Palliative care represents an important component of the holistic management of this disease.”

Looking to the future, Tulsky hopes this study will encourage HF programs to adopt palliative care treatment protocols, and that it will serve as strong support for a larger multicenter study.

This work was funded by the National Institute of Nursing Research.

Paper cited: Roger JG et al. “Palliative Care in Heart Failure. The PAL-HF Randomized, Controlled Clinical Trial” JACC DOI: 10.1016/j.jacc.2017.05.030