UA Researchers Add New Twist in Debate over Free Radicals, Antioxidants in Cardiovascular Health — Less Isn’t Necessarily More

Eliminating free radicals via anti-oxidative therapies in your diet doesn’t automatically equate to better health as it shifts the dietary balance to so-called “reductive” stress that can lead to inflammation with negative cardiovascular outcomes, particularly for men, UA researchers say.

Increased antioxidant levels in our diet could have negative outcomes that override their positive effect of removing free radicals, according to researchers at the University of Arizona College of Medicine – Tucson.

Dr. Olga Rafikova Olga Rafikova, MD, PhD, a research assistant professor in the Division of Translational and Regenerative Medicine at the UA College of Medicine – Tucson, will present on an abstract selected for oral presentation at the Society for Redox Biology and Medicine (SFRBM) 22nd annual meeting, Nov. 18-21, in Boston. Research behind that abstract adds a new twist in the antioxidant health trend of recent years. Dr. Rafikova will make her presentation on Saturday, Nov. 21, at about 3:45 p.m. (EDT) at the Westin Boston Waterfront Hotel, 425 Summer St.

Antioxidant therapy involves treating patients with natural vitamins and nutritional supplements to try to limit some degenerative medical conditions. Physicians are investigating ways to use this dietary or nutritional treatment to help patients combat a variety of illnesses, from diabetes to cardiovascular disease. Research, though, has not shown antioxidant supplements to be beneficial in preventing such diseases, according to the National Institutes of Health.

“Although in many studies antioxidants were found to be beneficial, this has not been confirmed in clinical settings,” Dr. Rafikova said. “At the University of Arizona, we uncovered one of the mechanisms that could be directly implicated in the problem with antioxidant therapy: The increased levels of antioxidants could have negative outcomes that override the positive effect of removing free radicals.”

Her research investigated the connection between oxidative-reductive balance and pulmonary hypertension for each gender, both in patients and animal models. What they found was that a shift toward a more reduced state that is associated with the male gender severely contributes to the progression of chronic disease by promoting inflammation and cardiac failure.

Dr. Ruslan Rafikov“It’s very new,” said Ruslan Rafikov, PhD, Dr. Rafikova’s husband, research colleague and also a UA assistant professor in the Division of Translational and Regenerative Medicine as well as the abstract’s senior author. “Nobody recognized it. Everyone is trying to treat oxidative stress, but here we have reductive stress. This is especially true for men because they seem to be more prone to reductive stress and inflammatory response that increases fibrosis of the lungs and heart, making male survival less than females. We’re still trying to find the clue for why men and women are different here. The one thing we learned from this study is that men and women should be treated differently, although they may have the same disease.”

Drs. Rafikova and Rafikov joined the Division of Translational and Regenerative Medicine, which last year became the newest division in the UA Department of Medicine, in February 2015.

Dr. Rafikova recently was among seven UA Health Sciences junior faculty members selected  for Career Development Awards due to their promising research. The SFRBM presentation is based on that research. Her SFRBM abstract, “Reductive stress associated with the male gender contributes to pulmonary hypertension and right ventricle dysfunction,” was co-written with Dr. Rafikov; Stephen M. Black, PhD, UA professor of medicine and director of the Lung Vascular Pathobiology Program; Ankit Desai, MD, UA assistant professor with the UA Sarver Heart Center’s Molecular Cardiovascular Research Program; Vineet Nair, MBBS, a research trainee in Dr. Desai’s lab; Kristina Skinner, DO, a resident physician in the UA College of Medicine – Tucson’s Internal Medicine Residency Program; and Morgan Whitaker, a second-year student at the UA College of Medicine – Tucson.

Dr. Rafikova is a graduate of Russia’s Moscow State University, where she earned her medical degree and a doctorate in physiology. She came to the United States in 2000 to study the role of free radical imbalance in myocardial infarction at New York University. In 2008, she completed a post-doctoral fellowship in cardiovascular hypertension at the University of Pittsburgh. She also did fellowships in vascular biology and cardio-renal biology at the Medical College of Georgia, now Georgia Regents University, in Augusta.

Before coming to the UA, Dr. Rafikov completed a fellowship at Georgia Regents University, where he also was an assistant research scientist studying cardiovascular diseases. Prior to that, he was a postdoctoral fellow at the University of Pittsburgh and a research associate at New York University. He holds a doctorate in biophysics from the Biochemical Physics Institute in Moscow and a master’s degree in chemistry from Moscow State University. In 2014, he received a four-year American Heart Association Scientist Development Grant.

Dr. Rafikov also has four SFRBM 2015 poster presentations:

  • “Complex I dysfunction dictates glycolytic switch in pulmonary hypertensive smooth muscle cells”
  • “Metabolic changes precede the development of pulmonary hypertension in monocrotaline model”
  • “Bio-catalysis of heme extraction from extracellular hemoglobin for Sickle Cell Disease and hemolysis treatments”
  • “Targeted protein protection from oxidative/nitrosative post-translational modifications using shielding peptides”

The SFRBM is a professional organization of scientists and clinicians with an interest in the research and medical applications of free radical chemistry, redox biology and antioxidants. The annual meeting is the premier venue for cutting-edge research in all aspects of redox biology and antioxidants. It features the latest technologies and applications in basic and translational research. Scientists in all phases of their research careers — students and seasoned investigators alike — will share their findings in the field of redox biology, which can have relevant implications on health, medicine and everyday life.