(Press-News.org)
Embargoed for release: Thursday, June 5, 4:00 PM ET
Key points:
Nearly one-third of nutrition clinical trial participants who adopted and adhered to a healthy diet did not lose any weight, but still saw significant improvements to their cardiometabolic health, including higher HDL cholesterol, lower levels of leptin, and less visceral fat.
The findings demonstrate that individuals resistant to weight loss may still achieve meaningful health benefits with lifestyle changes.
Cutting-edge omics tools revealed 12 specific DNA methylation sites that strongly predict long-term weight loss—a novel finding that shows how some people may be biologically wired to respond differently to the same diet.
Boston, MA—Nearly one-third of people who adopted and adhered to a healthy diet did not lose any weight, but still reaped many health benefits, according to a new study led by researchers at Harvard T.H. Chan School of Public Health and Ben Gurion University, Israel. Independent of weight reduction, study participants showed significant improvements in cardiometabolic markers, including higher HDL cholesterol (the healthy type of cholesterol), lower levels of leptin (the hormone that signals hunger), and less visceral fat (belly fat found deep inside the abdominal cavity, sometimes wrapping around organs).
“We have been conditioned to equate weight loss with health, and weight loss-resistant individuals are often labeled as failures,” said lead author Anat Yaskolka Meir, postdoctoral research fellow in the Department of Epidemiology at Harvard Chan School. “Our findings reframe how we define clinical success. People who do not lose weight can improve their metabolism and reduce their long-term risk for disease. That’s a message of hope, not failure.”
The study will be published June 5 in the European Journal of Preventive Cardiology.
The researchers analyzed changes in weight and health among 761 individuals with abdominal obesity in Israel who participated in three landmark workplace-based nutrition clinical trials (DIRECT, CENTRAL, and DIRECT-PLUS) with high adherence rates and comprehensive metabolic profiling. At each trial, participants were randomly assigned to adopt and adhere to healthy diets—including low-fat, low-carbohydrate, Mediterranean, and green-Mediterranean diets—for between 18 and 24 months.
The study found that, across all of the clinical trials and all of the diets, 36% of participants achieved clinically significant weight loss (defined as losing more than 5% of their initial body weight); 36% achieved moderate weight loss (losing up to 5% of their initial body weight); and 28% were resistant to weight loss, losing no weight or gaining some. Weight loss was associated with a variety of health improvements: The researchers calculated that each kilogram lost was associated with a 1.44% increase in HDL cholesterol, a 1.37% decrease in triglycerides, a 2.46% drop in insulin, a 2.79% drop in leptin, and a 0.49-unit reduction in liver fat, along with reductions in blood pressure and liver enzymes.
The study also found, however, that participants who were resistant to weight change—who tended to be older and/or women—showed many of the same improvements. They had more good cholesterol; lower levels of leptin, leading to less hunger; and less harmful visceral fat.
“These are deep metabolic shifts with real cardiometabolic consequences,” said Yaskolka Meir. “Our study showed that a healthy diet works, even when weight doesn’t shift.”
The researchers also utilized cutting-edge omics tools and discovered 12 specific DNA methylation sites that strongly predict long-term weight loss.
“This novel finding shows that some people may be biologically wired to respond differently to the same diet,” said corresponding author Iris Shai, principal investigator of the nutrition trials and adjunct professor of nutrition at Harvard Chan School. “This isn’t just about willpower or discipline—it’s about biology. And now we’re getting close to understanding it.”
The study had some limitations, namely that the majority of participants were men. The researchers noted that future similar studies should focus on women.
Other Harvard Chan co-authors included Lu Qi, Dong Wang, Liming Liang, Frank Hu, and Meir Stampfer.
The study was funded by the German Research Foundation (project 209933838).
“Individual Response to Lifestyle Interventions: A Pooled Analysis of Three Long-Term Weight Loss Trials,” Anat Yaskolka Meir, Gal Tsaban, Ehud Rinott, Hila Zelicha, Dan Schwarzfuchs, Yftach Gepner, Assaf Rudich, Ilan Shelef, Matthias Blüher, Michael Stumvoll, Uta Ceglarek, Berend Isermann, Nora Klöting, Maria Keller, Peter Kovacs, Lu Qi, Dong D. Wang, Liming Liang, Frank B. Hu, Meir J. Stampfer, Iris Shai, the European Journal of Preventive Cardiology, June 5, 2025, doi: 10.1093/eurjpc/zwaf308
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Harvard T.H. Chan School of Public Health is a community of innovative scientists, practitioners, educators, and students dedicated to improving health and advancing equity so all people can thrive. We research the many factors influencing health and collaborate widely to translate those insights into policies, programs, and practices that prevent disease and promote well-being for people around the world. We also educate thousands of public health leaders a year through our degree programs, postdoctoral training, fellowships, and continuing education courses. Founded in 1913 as America’s first professional training program in public health, the School continues to have an extraordinary impact in fields ranging from infectious disease to environmental justice to health systems and beyond.
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EMBARGOED UNTIL Thursday, 5 June 2025 at 14:00 (2:00 pm) U.S. Eastern Time (8pm South Africa time, 7pm UK time)
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