Bringing precision to the murky debate on fish oil

The nutritional good-for-you, bad-for-you tug-of-war on fish oil has left a lot of room for confusion, but University of Arizona precision nutrition researcher Floyd "Ski" Chilton believes there may be overlooked explanations: ancestry and related genetics. 

"We're in the middle of a precision revolution. It largely started with cancer, moved to other fields of medicine, and now has found its way to nutrition," he said.

The rapidly expanding field of precision nutrition draws on multiple scientific disciplines including evolutionary biology, nutrition, genetics, data science, and bioinformatics to provide personalized dietary guidance based on an individual's genetic makeup, environment and lifestyle. 

Chilton, a professor of nutritional sciences in the College of Agriculture, Life and Environmental Sciences and a member of the university's BIO5 Institute, has been an early champion in the field of precision nutrition, and now, with a $3.9 million grant from the National Institutes of Health, he aims to bring precision to the fish oil debate. 

With colleagues from the U of A, Georgetown University and the MedStar Health Research Institute in Maryland, Chilton will carry out a clinical trial investigating how ancestry and genetics shape the body's response to omega-3 fatty acids.   

Addressing knowledge gaps, health disparities

The new clinical trial will build on Chilton and his collaborators' reanalysis of data provided from the landmark VITAL study – a large-scale clinical trial spanning five years and involving more than 25,000 participants. The study sought to investigate whether taking daily supplements of vitamin D and omega-3 fatty acids could reduce risk of cancer and cardiovascular disease, including heart attack and stroke, in people without a history of these illnesses. 

Initial results and media coverage from the 2018 study reported no significant overall benefit from fish oil supplementation, but that broad-stroke interpretation overshadowed significant fish oil benefits found among the 5,100 African American participants in the study, Chilton said. 

While not the specific focus of the clinical trial, data collected through the VITAL study suggested there was a marked reduction, 77%, in heart attacks among African American participants taking omega-3 supplements. 

"The VITAL investigators should be congratulated for including more African American participants than all other omega-3 trials combined," said Jason Umans, co-author of the reanalysis and member of the Georgetown-Howard Universities Center for Clinical and Translational Science. 

"But the original analysis identified the possibility of a selective benefit to African Americans and our reanalysis suggests the likelihood that African Americans are being denied a uniquely beneficial preventive treatment, simply because it did not work in the larger number of Non-Hispanic White trial participants," Umans said. 

Using aplied mathematics models, U of A and Georgetown researchers reanalyzed the VITAL data to focus specifically on how genetic ancestry impacted effectiveness of omega-3 supplementation. Initially, they clinically matched 3,766 African American participants with 3,766 non-Hispanic white participants across 13 different variables – including sex, age, medication, medical history and fish consumption. Machine learning was then used to simulate clinical trial conditions within these groups, assessing the risk of heart attack, stroke, and cardiovascular disease mortality associated with omega-3 supplementation.

“When you clear away all the noise that you had there before, the apparent benefit of omega-3 supplementation in African American participants is even bigger, 83%. The decrease in heart attacks was not just large, it was huge," Umans said. 

"This new clinical study along with our work over the past 15 years strongly suggest that ancestral and associated genetic differences affect the levels and balance of omega-6 and omega-3 fatty acids in the human body, and this balance is critical to maintain cardiovascular health," Chilton said. "Collectively, this work sets the stage for the new NIH-funded study, which aims to investigate these benefits further."

The researchers say their continued work to sort out the mechanisms that may link genetic variation and omega-3 fatty acid effects could identify other populations who, like African Americans, would benefit from omega-3 supplementation. 

"The research underscores the limitations of a one-size-fits-all approach to nutrition," Chilton said, "and it's paving the way for a precision nutrition revolution, promising more effective disease prevention tailored to our genetic profiles."

The $3.9 million NIH grant "Addressing Diet-Induced Health Disparities with Precision Nutrition and Omega-3 Fatty Acids" is a collaborative involving the U of A, Georgetown University and MedStar Health Research Institute. It is led by principal investigators Chilton; Cynthia Thomson, a professor in the Mel and Enid Zuckerman College of Public Health; and Susan Schembre, an associate professor at Georgetown, with support from Umans; Brian Hallmark, an assistant research professor with BIO5; Dawn Coletta, an associate professor with the College of Medicine – Tucson; and Chiranjeev Dash, assistant director of health disparities research at Georgetown.