Applying to medical school is an undeniably complicated process, but Azan Virji discovered that it’s even tougher when you’re an international student.

The Tanzanian applicant’s options were slim, even though he already had a bachelor’s and a master’s in public health from Yale. Only 48 American institutions consider international applicants, and they accept them at about half the rate of U.S. citizens. And he had no idea about how to go about applying for financial aid.

“When I was applying to medical school, I had no one to talk to as an international, as someone applying to medical school, as someone seeking financial aid,” said Virji, now in his second year at Harvard Medical School. “Always in the back of my mind, I thought, ‘If I get in, I’ll do something about this.’” Thus was born the idea for F-1 Doctors, a group of international med students who offer help to applicants facing the same challenges they did.

Virji founded the organization with Ghazal Aghagoli, an Iranian/Canadian student, and Ben Gallo Marin from Nicaragua. Both are students at Brown University’s Warren Alpert Medical School. Currently there are 70 volunteers from 30 countries who’ve helped more than 60 students.

Through its website, F-1 Doctors offers a host of resources to international students interested in going to a U.S. medical school: links to guides on admissions and on taking the Medical College Admission Test, or MCAT. The organization offers information on financial aid, has hosted webinars on the admissions process, and made links to past webinars available.

In addition to offering professional guidance, group members also offer personal support, which has been particularly necessary amid the political turmoil of recent years. Many international applicants have had to deal with the fallout from the anti-immigrant climate fostered by the Trump administration, particularly involving those from Latin America, China, and predominantly Muslim countries. The hostile rhetoric was matched by action when the White House restricted travelers from Tanzania earlier this year, and then suspended issuing H-1 work visas — which graduating students need to get jobs legally after their F-1 student visas expire. (The group takes its name from the visa designation.)

Eating milk chocolate every day may sound like a recipe for weight gain, but a new study of postmenopausal women has found that eating a concentrated amount of chocolate during a narrow window of time in the morning may help the body burn fat and decrease blood sugar levels.

Harvard Medical School professor of medicine Frank A.J.L. Scheer and Marta Garaulet, both of the Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology at Harvard-affiliated Brigham and Women’s Hospital, are co-corresponding authors of the new paper published in The FASEB Journal.

To find out about the effects of eating milk chocolate at different times of day, researchers from the Brigham collaborated with investigators at the University of Murcia in Spain. Together, they conducted a randomized, controlled, cross-over trial of 19 postmenopausal women who consumed either 100g of chocolate in the morning (within one hour after waking time) or at night (within one hour before bedtime). They compared weight gain and many other measures to no chocolate intake.

Researchers report that among the women studied:

• Morning or nighttime chocolate intake did not lead to weight gain;
• Eating chocolate in the morning or in the evening can influence hunger and appetite, microbiota composition, sleep and more;
• A high intake of chocolate during the morning hours could help to burn fat and reduce blood glucose levels.
• Evening/night chocolate altered next-morning resting and exercise metabolism.

“Our findings highlight that not only ‘what’ but also ‘when’ we eat can impact physiological mechanisms involved in the regulation of body weight,” said Scheer.

“Our volunteers did not gain weight despite increasing caloric intake. Our results show that chocolate reduced ad libitum energy intake, consistent with the observed reduction in hunger, appetite and the desire for sweets shown in previous studies,” said Garaulet.

This work was supported in part by Ministry of Science, Innovation and Universities (MICINN) (SAF2017-84135-R) including FEDER co-funding; The Autonomous Community of the Region of Murcia through the Seneca Foundation (20795/PI/18) and NIDDK R01DK105072 granted to M.G.; M.C.C. acknowledges the support from the Ministry of Science, Innovation and Universities (MICINN) (RTI2018-097982-B-I00); F.A.J.L.S. was supported in part by NIH grants R01HL094806, R01HL118601, R01DK099512, R01DK102696, and R01DK105072 (to F.A.J.L.S.)

Tracie Jones turned to a librarian friend, Sarah DeMott, for help documenting the experience of Black Americans in the age of COVID-19.

A few Zoom sessions and emails later, Jones and DeMott created Black America and COVID-19, a library guide that aims to serve as a historical record and shed light on the pandemic’s impact on African Americans, who are twice as likely to die from the disease than whites, according to the COVID Tracking Project.

“In 10 or 15 years from now, researchers and the general public can look at the guide and learn from scholarly and non-scholarly pieces what it was like to be a Black person in the time of COVID-19,” said Jones, the director of diversity, inclusion, and belonging at the Graduate School of Education. “It’s an important record. The racial disparities of COVID-19 are something we need to talk about as a larger community.”

The guide began taking shape in March when Jones and DeMott started collecting material from the Internet, including news articles and cultural artifacts such as songs, videos, and personal narratives that were predominant in the early days of the pandemic. Research papers and peer-reviewed articles were hard to come by in those days, as scientists were busy dealing with the outbreak. But the goal was to capture the personal stories as they were unfolding.

“We didn’t want the ephemerality of the situation to escape,” said DeMott, research librarian at Harvard College Library. “We wanted to make sure that all those accounts didn’t disappear. We were trying to capture the feeling on the ground at the moment.”

Included in the guide are recordings of incarcerated women complaining about the lack of cleaning supplies and sanitizers, videos of online town hall discussions about the impact of the outbreak on Black communities, podcasts, blog posts, links to webinars, and even a clip of Cardi B’s viral “Coronavirus (S*t Is Real)” remix.

Black America and COVID-19 organizes the material by themes such as health, data, youth, community activism, music, and poetry and literature, among others. Each theme has a co-curator who advises on content. Many of them are African American and experts in their field. The guide strives to be a collaborative platform and welcomes contributions from researchers, faculty, students, and the general public.

Jo Persad ’21, a master’s student at the Ed School, said that she joined the guide as an intern in July because it offered a rare chance to participate in a project in which the Black community, instead of outsiders, documented its own history of a major event.

“As a Black woman myself, it just felt it was an amazing opportunity to be part of preserving the Black experience of this pandemic,” said Persad. “Too often when we think about the Black experience, we think about somebody who is white who comes in, does an interview, and writes up his or her own interpretation. In our library guide, there are Black people who are co-curators and are deciding what should be preserved.”

Jones and DeMott hope the guide can become a platform to spawn a civic dialogue about the role of institutional racism in the disproportionate rates of COVID-19 among Black communities in the U.S.

With support from the Harvard Libraries, the Office of Diversity, Inclusion & Belonging, and the Charles Hamilton Houston Institute for Race and Justice at Harvard Law School, the guide employs four student interns who lead workshops, community discussions, and an anti-racism book and film club. Persad is spearheading blackcovidtales on Instagram to collect individual accounts of life as a Black person in Tik Tok videos, journals, raps, photographs, etc.

The death of a family pet can trigger a sense of grief in children that is profound and prolonged, and can potentially lead to subsequent mental health issues, according to a new study by researchers at Massachusetts General Hospital (MGH).

In a paper appearing in European Child & Adolescent Psychiatry, the team found that the strong emotional attachment of youngsters to pets might result in measurable psychological distress that can serve as an indicator of depression in children and adolescents for as long as three years or more after the loss of a beloved pet.

“One of the first major losses a child will encounter is likely to be the death of a pet, and the impact can be traumatic, especially when that pet feels like a member of the family,” said Katherine Crawford, previously with the Center for Genomic Medicine at MGH, and lead author of the study. “We found this experience of pet death is often associated with elevated mental health symptoms in children, and that parents and physicians need to recognize and take those symptoms seriously, not simply brush them off.”

Roughly half of households in developed countries own at least one pet. And as the MGH investigators reported, the bonds that children form with pets can resemble secure human relationships in terms of providing affection, protection and reassurance. Previous studies have shown that children often turn to pets for comfort and to voice their fears and emotional experiences. While the increased empathy, self-esteem and social competence that often flow from this interaction is clearly beneficial, the downside is the exposure of children to the death of a pet which, the MGH study found, occurs with 63 percent of children with pets during their first seven years of life.

Prior research has focused on the attachment of adults to pets and the consequences of an animal’s death. The MGH team is the first to examine mental health responses in children. Their analysis is based on a sample of 6,260 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), in Bristol, England. This population-based sample is replete with data collected from mothers and children that enabled researchers to track the experience of pet ownership and pet loss from a child’s early age up to eight years.

“Thanks to this cohort, we were able to analyze the mental and emotional health of children after examining their experiences with pet death over an extended period,” said Erin Dunn, with the MGH Center for Genomic Medicine and Department of Psychiatry, and senior author of the study. “And we observed that the association between exposure to a pet’s death and psychopathology symptoms in childhood occurred regardless of the child’s socio-economic status or hardships they had already endured in their young lives.”

Researchers also learned that the relationship between pet death and increased psychopathology was more pronounced in male than female children — a finding that surprised them in light of prior research — and that the strength of the association was independent of when the pet’s death occurred during childhood, and how many times or how recently it occurred. According to Dunn, this latter finding speaks to “the durability of the bond with pets that is formed at a very early age, and how it can affect children across their development.”

The MGH study stressed the importance of parents, caregivers and pediatricians recognizing and taking seriously the short- and long-term psychological reactions of children to the death of a pet — reactions which can mimic a child’s response to the loss of other important family members. “Adults need to pay attention to whether those feelings are deeper and more profound and if they’re lasting longer than might have been expected,” says Crawford. “They could be signs of complicated grief and having someone to talk to in a sympathetic or therapeutic way may be extremely helpful for a child who is grieving.”

Lead author Crawford is a genetic counselor previously with the Center for Genomic Medicine, MGH, now at Women & Infants Hospital of Rhode Island. Senior author Dunn is assistant professor with the Psychiatric and Neurodevelopmental Genetics Unit, in the Center for Genomics Medicine, and the Department of Psychiatry. Co-author Yiwen Zhu is a data analyst in the Center for Genomic Medicine.

Researchers at Harvard University and the Broad Institute of MIT and Harvard have created a detailed atlas of a critical region of the developing mouse brain, applying multiple advanced genomic technologies to the part of the cerebral cortex that is responsible for processing sensation from the body. By measuring how gene activity and regulation change over time, researchers now have a better understanding of how the cerebral cortex is built, as well as a brand new set of tools to explore how the cortex is affected in neurodevelopmental disease. The study is published in the journal Nature.

“We have had a long-standing interest in understanding the development of the mammalian cerebral cortex, as it is the seat of higher-order cognition and the part of the brain that has expanded and diversified the most during human evolution,” said Paola Arlotta, the co-senior author of the study and the Golub Family Professor of Stem Cell and Regenerative Biology at Harvard University. “In this study, we looked at the cortex with a very fine lens, practically profiling all of its cells, one by one, every day of development. We cataloged changes in gene expression and regulation at an unprecedented level of temporal resolution to build a first single-cell-resolution molecular map of this amazing tissue. The map allowed us to extract first mechanistic principles governing how the cortex is built, and begin to decode how genetic abnormalities affect such highly controlled process in the embryo.”

“In the developing brain, we have to consider three things: the types of cells that are present, where those cells are located, and at what stage they are in development. In addition, by identifying the drivers that direct this process in normal development, we can better understand what may go wrong in disease,” said co-senior author Aviv Regev, who was a core institute member at the Broad Institute when the study began and is currently Head of Genentech Research and Early Development.

The researchers focused on the somatosensory cortex, which may serve as a model for other regions of the cerebral cortex because it contains cells representing all of its major classes. For every day of cortex development, the researchers analyzed the brain using multiple technologies at the single-cell level. They used RNA-seq to measure which genes are expressed, as well as spatial transcriptomics to measure where genes are expressed in the tissue. They also used ATAC-seq to measure which parts of the genome were accessible for regulation.

“These technologies allowed us to look at different modes of gene expression and how genes are regulating each other. By combining these three modalities, we have a stronger sense of which are the important genes for directing neuronal development, for example” said Daniela Di Bella, a postdoctoral fellow in the Arlotta lab and co-first author of the study.

For instance, it has been unclear exactly when the cortex’s diversity of different neuron populations is established. “We found that the different flavors of neurons are decided during the neuron maturation process, rather than pre-established in their stem cells,” Di Bella said.

The researchers also used their data to predict the underlying mechanism of how genetic mutation leads to defects in cortical development, finding which specific developmental steps are failing and which cells are being affected.

“We have created a uniquely comprehensive molecular atlas of the developing somatosensory cortex, and we are continuing to mine the data for more insights,” said co-first author Ehsan Habibi. “Our goal is for our data to serve as a resource for the wider neuroscience community and inform how the field looks at brain development, both during normal and disease processes.”

“These combined, extensive measurements provided us with a first dynamic view of the symphony of molecular events that unfold as this critical region of the brain is built in the embryo,” said Arlotta, who is also an institute member in the Stanley Center for Psychiatric Research at the Broad Institute. “Researchers have been studying the process of development of the cerebral cortex for over a century, but the mechanistic events that govern how cells are made and how they interact to ultimately form functional circuit have remained elusive. As a field, we have historically looked at this complex developing tissue one cell type at a time and investigated small numbers of genes for their roles in putting together pieces of this amazing puzzle. But the brain does not develop one cell type at the time — it is truly a symphony in the sense that hundreds of cell types undergo development together, using ever-changing landscapes of genes to form the adult tissue. Now imagine having for the first time the full ‘recipe’ of genes that any given cell class uses as its development unfolds. Imagine also gaining detailed knowledge of the ‘codes of genes’ that turn on or off as distinct lineages of cells separate from each other and get built. This type of overarching mechanistic knowledge offers an opportunity to study cortical development in a brand new way, looking at all cells and all genes. We never had information this complete before and I must admit that I stared at the data in awe, thinking about the type of discovery that it enables.”

“Ten years ago, this study would not have been possible because the technologies either did not exist or were not mature enough yet,” Regev said. “But with advances in single-cell and spatial transcriptomics, and new machine learning algorithms for large data analysis, we were able to map where cells develop, put those maps together, and watch development unfold like a movie over time. We could not only reconstruct the movie but could also link that picture to a greater biological understanding of brain development. We hope this approach could one day help us better understand and treat diseases of the brain.”

Arlotta added: “It is a pretty interesting movie — one that I have looked forward to filming for most of my scientific career.”

This research was supported by the Stanley Center for Psychiatric Research, the Broad Institute of MIT and Harvard, the P50 Conte Center (5P50MH094271 Developmental origins of mental illness: evolution and reversibility), the National Institutes of Health (5U19MH114821, 5R01NS103758, DP5OD024583), the Klarman Cell Observatory, HHMI, and an NHGRI Center for Cell Circuits CEGS grant.

The pandemic may be easing, but a new set of emotional challenges has only just begun.

One worker got the green light to return to the office but found herself sitting in the parking lot each day, hyperventilating in her car, before summoning the courage to head in. Another questioned whether a normal back-to-school this fall — the moment many parents, if not their kids, have awaited more than a year — might be stressful enough to harm some students’ mental health. A third asked how he might get an appointment with a counselor in an era of soaring demand. The unfortunate answer was that many providers are full. And waitlists are so jammed that some are closing to new patients.

Psychologists, psychiatrists, and counselors have long predicted that once the pandemic’s acute phase eased and its physical impacts lessened, there would be mental health fallout. Though the virus continues to rage abroad — the highly contagious delta variant has triggered new shutdowns in several nations, including Australia, South Africa, and Thailand — the widespread availability of vaccines in the U.S. have meant large swaths of the country can tentatively return to whatever remains of “normal.” And Karestan Koenen, a professor of psychiatric epidemiology at the Harvard T.H. Chan School of Public Health, has some advice: Go slowly.

Koenen, who appeared at a Chan School live event on Facebook on June 29, said attempts to return to pre-pandemic routines may feel unsettling and fielded questions about specific situations from the online audience. Working against us, Koenen said, is that many of us are eager to go back to the way things were exactly but will find that impossible. Given the extent of the pandemic’s effects, it’s understandable that the commute will be different, that employers will have new policies in place, and that workers’ home lives — obligations to children, parents, and spouses — will have shifted. All the change, Koenen said, can cause a sense of dislocation.

“Now, after hunkering down, when you go outside that can feel threatening,” Koenen said. “There also can be almost a grief or sadness because things that were normal don’t feel the same … I think that’s part of the changes we’re all going through right now.”

Koenen pointed out that even before the pandemic any change — even a positive one like getting married or starting a dream job — was known to be a stressor. Add to that the pandemic’s considerable stress, and the next few months will likely be challenging. For specific populations who may have isolated a lot during the pandemic, who may be experiencing anxiety about return to work, or who had pre-existing social anxiety, she suggested taking it a step at a time: Have lunch with a friend before going to a party; go to work for a few days a week before jumping back in full-time. Employers should recognize that the coming months may be difficult for workers and provide flexibility and encouragement if an employee needs to ease back in.

“We’ve all gone through a tremendous amount of change and stress this past year, in lockdowns, in changes to the way we work, live, in every aspect of our lives. And now we’re being asked to change back,” Koenen said. “It’s a time of tremendous change, and it’s good to remind ourselves that all change is stressful.”

Koenen said it’s also important, however, for individuals to recognize that avoidance enhances anxiety, so it’s best that — as long as infection rates remain low — they push their boundaries, even if, at first, they may feel heightened anxiety.

Looking ahead to the school year, Koenen said different schools have had different pandemic experiences, with some never halting in-person learning and others predominantly delivering instruction online. It’s likely that students who have been mostly remote will have a more difficult transition to the classroom this fall, and Koenen recommended that teachers locate referral resources for families in advance and keep an eye out for signs that a child is having trouble readjusting. Koenen also had advice for teachers and school administrators, who have had an enormously stressful year navigating the disruption: Take a vacation.

COVID-weary Americans hanging on to the hope for a vaccine by year’s end and a quick return to pre-pandemic normality should get used to the idea that it could take some time before enough Americans are immunized, for a number of reasons, including skepticism over the treatment.

“The most important ingredient in all vaccines is trust,” said Barry Bloom, the Joan L. and Julius H. Jacobson Research Professor of Public Health at the Harvard T.H. Chan School of Public Health. “Without trust a vaccine doesn’t do much good in the world.”

Bloom, with co-authors Glen Nowak of the University of Georgia and Walter Orenstein of Emory University’s School of Medicine, wrote a recent “Perspective” article in the New England Journal of Medicine calling for a major effort to build public trust in an eventual vaccine. The three say that the gap between the 50 percent of Americans who’ve said they’d accept a COVID-19 vaccine and the 60 to 70 percent believed needed to reach the threshold for “herd immunity” — at which enough people are immune that transmission is interrupted — “will take substantial resources and active, bipartisan political support to achieve the uptake levels needed.” The estimated shortfall amounts to about 33 to 66 million Americans.

Bloom, former dean of the Harvard Chan School, said in remarks to the media on Monday that misinformation distributed through social media and recent public tussles over the effectiveness of COVID treatments like hydroxychloroquine (which was granted emergency-use authorization, later revoked) have undermined public trust that vaccine candidates will be rigorously studied and widely administered only when determined safe and effective, without regard to political, economic, or other concerns.

In a large group of patients with metastatic colorectal cancer, consumption of a few cups of coffee a day was associated with longer survival and a lower risk of the cancer worsening, researchers at Harvard-affiliated Dana-Farber Cancer Institute and other organizations report in a new study.

The findings, based on data from a large observational study nested in a clinical trial, are in line with earlier studies showing a connection between regular coffee consumption and improved outcomes in patients with non-metastatic colorectal cancer. The study is being published today by JAMA Oncology.

The investigators found that in 1,171 patients treated for metastatic colorectal cancer, those who reported drinking two to three cups of coffee a day were likely to live longer overall, and had a longer time before their disease worsened, than those who didn’t drink coffee. Participants who drank larger amounts of coffee — more than four cups a day — had an even greater benefit in these measures. The benefits held for both caffeinated and decaffeinated coffee.

The findings enabled investigators to establish an association, but not a cause-and-effect relationship, between coffee drinking and reduced risk of cancer progression and death among study participants. As a result, the study doesn’t provide sufficient grounds for recommending, at this point, that people with advanced or metastatic colorectal cancer start drinking coffee on a daily basis or increase their consumption of the drink, researchers say.

“It’s known that several compounds in coffee have antioxidant, anti-inflammatory, and other properties that may be active against cancer,” says Dana-Farber’s Chen Yuan, the co-first author of the study with Christopher Mackintosh of the Mayo Clinic School of Medicine. “Epidemiological studies have found that higher coffee intake was associated with improved survival in patients with stage 3 colon cancer, but the relationship between coffee consumption and survival in patients with metastatic forms of the disease hasn’t been known.”

The new study drew on data from the Alliance/SWOG 80405 study, a phase III clinical trial comparing the addition of the drugs cetuximab and/or bevacizumab to standard chemotherapy in patients with previously untreated, locally advanced or metastatic colorectal cancer. As part of the trial, participants reported their dietary intake, including coffee consumption, on a questionnaire at the time of enrollment. Researchers correlated this data with information on the course of the cancer after treatment.

They found that participants who drank two to three cups of coffee per day had a reduced hazard for death and for cancer progression compared to those who didn’t drink coffee. (Hazard is a measure of risk.) Those who consumed more than four cups per day had an even greater benefit.

“Although it is premature to recommend a high intake of coffee as a potential treatment for colorectal cancer, our study suggests that drinking coffee is not harmful and may potentially be beneficial,” says Dana-Farber’s Kimmie Ng, senior author of the study.

“This study adds to the large body of literature supporting the importance of diet and other modifiable factors in the treatment of patients with colorectal cancer,” Ng adds. “Further research is needed to determine if there is indeed a causal connection between coffee consumption and improved outcomes in patients with colorectal cancer, and precisely which compounds within coffee are responsible for this benefit.”

Funding for the study was provided by the National Cancer Institute (grants U10CA180821, U10CA180882, U10CA180795, U10CA180838, U10CA180867, U24CA196171, UG1CA189858, P50CA127003, R01CA118553, R01CA205406, U10CA180826, U10CA180830, and U10CA180888), the Project P Fund, Genentech, Sanofi, and Pfizer.

A skin pigmentation mechanism that can darken the color of human skin as a natural defense against ultraviolet (UV)-associated cancers has been discovered by scientists at Harvard-affiliated Massachusetts General Hospital (MGH). Mediating the biological process is an enzyme called nicotinamide nucleotide transhydrogenase (NNT), which plays a key role in the production of melanin (a pigment that protects the skin from harmful UV rays). Its inhibition through a topical drug or ointment could potentially reduce the risk of skin cancers, as presented in a study in Cell.

“Skin pigmentation and its regulation are critically important because pigments confer major protection against UV-related cancers of the skin, which are the most common malignancies found in humans,” says senior and co-corresponding author David Fisher, chief of the Department of Dermatology at MGH. “Darker-pigmented individuals are better protected from cancer-causing UV radiation by the light-scattering and antioxidant properties of melanin, while people with the fairest and lightest skin are at highest risk of developing skin cancers.”

Through their laboratory work with skin from humans and animal models, the MGH researchers mimicked the natural protection that exists in people with dark pigments. In the process, they gained a fuller understanding of the biochemical mechanism involved, along with their drivers and how they might be influenced by a topical agent independent of UV radiation, sun exposure, or genetics.

“We had assumed that the enzymes that make melanin by oxidizing the amino acid tyrosine in the melanosome (the synthesis and storage compartment of the cell) are largely regulated by gene expression,” explains Fisher. They were surprised to learn, however, that the amount of melanin being produced is in large part regulated by a much different chemical mechanism, one that can ultimately be traced to NNT in the mitochondria, the inner chamber of the cell, with the ability to alter skin pigmentation.

Researchers found that topical application of small molecule inhibitors of NNT resulted in skin darkening in human skin, and mice with decreased NNT function displayed increased fur pigmentation. To test their discovery, they challenged the skin with UV radiation and found that the skin with darker pigments was indeed protected from DNA damage inflicted by ultraviolet rays.

“We’re excited by the discovery of a distinct pigmentation mechanism because it could pave the way, after additional studies and safety assessments, for a new approach to skin darkening and protection by targeting NNT,” says Elisabeth Roider, previously an investigator with MGH, and lead author and co-corresponding author of the study. “The overarching goal, of course, is to improve skin cancer prevention strategies and to offer effective new treatment options to the millions of people suffering from pigmentary disorders.”

Fisher is a professor of Dermatology and Pediatrics at the Harvard Medical School and director of both the Cutaneous Biology Research Center and Melanoma Center at MGH. Roider is an attending physician in the Department of Dermatology at the University Hospital of Basel, Switzerland, and a visiting scientist at the Cutaneous Biology Research Center at MGH.

In 2018, a study found that a high dose of an omega-3 fatty acid given to patients with an elevated cardiac risk significantly reduced cardiovascular events.

Findings from the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) were published in the New England Journal of Medicine. This helped the prescription drug icosapent get approved by the U.S. Food and Drug Administration, Health Canada, and European Medicines Agency to reduce cardiovascular risk in patients with elevated triglycerides. However, subsequent studies of supplements that combine purified ethyl ester of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have had mixed results.

Deepak L Bhatt, executive director of Interventional Cardiovascular Programs at the Brigham and lead investigator of the REDUCE-IT trial, along with colleagues at Harvard-affiliated Brigham and Women’s Hospital, performed a meta-analysis of 38 randomized clinical trials of omega-3 fatty acids, including trials of EPA monotherapy and EPA+DHA therapy. These showed higher relative reductions in cardiovascular outcomes using only EPA.

“REDUCE-IT has ushered in a new era in cardiovascular prevention,” said Bhatt. “REDUCE-IT was the largest and most rigorous contemporary trial of EPA, but there have been other ones as well. Now, we can see that the totality of evidence supports a robust and consistent benefit of EPA.”

In total, these trials included more than 149,000 participants. They evaluated key cardiovascular outcomes, including cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation. Overall, omega-3 fatty acids reduced cardiovascular mortality and improved cardiovascular outcomes.

The researchers note that there are crucial biological differences between EPA and DHA. While both are considered omega-3 fatty acids, they have different chemical properties that influence their stability and the effect that they can have on cholesterol molecules and cell membranes. No trials to date have studied the effects of DHA alone on cardiovascular outcomes.

“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically prescription EPA,” said Bhatt. “It should encourage investigators to explore further the cardiovascular effects of EPA across different clinical settings.”

REDUCE-IT was sponsored by Amarin. Brigham and Women’s Hospital receives research funding from Amarin for the work Bhatt did as the trial chair and as the international principal investigator. The present analysis was unfunded.