Examining the Impact of Carbohydrate Overfeeding on Metabolic Dysfunction

Close up of processed foods like pretzels, cookies, potato chips

For decades, researchers have emphasized the importance of reducing dietary fat intake to prevent obesity. The role of excess carbohydrate consumption has received comparatively little attention.

Two Brigham and Women’s Hospital obesity medicine specialists, Nawfal W. Istfan, MD, PhD, a physician in the Center for Weight Management and Wellness, and Caroline M. Apovian, MD, co-director of the center, are seeking to rectify this oversight. In a paper published in the American Journal of Physiology-Endocrinology and Metabolism, they and their colleagues explore the impact of acute carbohydrate overfeeding (COF) on metabolic dysfunction.

Their findings were highlighted in a recent Brigham Research Brief.

To study how cells break down carbohydrates in real time, the investigators studied the effects of COF in healthy normal weight and healthy overweight participants. They found that excess carbohydrates can contribute to metabolic dysfunction by blocking the synthesis of important antioxidants. Furthermore, they demonstrated that high insulin levels under such circumstances can exacerbate the issue.

“When we treat people with type 2 diabetes, the focus is often on lowering blood sugar rather than preventing carbohydrate overfeeding, which is very common in our society,” Dr. Istfan says. “But our study shows that if overfeeding isn’t controlled, some of the traditional ways of treating diabetes, like giving patients more insulin to lower blood sugar, can potentially be more harmful.”

Insulin May Contribute to Metabolic Distress

The investigators tracked the activity of the electrons in the cells of 24 non-diabetic human subjects with and without obesity as they were being overfed carbohydrates in the form of sugar. In addition, participants adhered to a very high-carbohydrate diet for several days prior to the monitoring study and then had their insulin sensitivity evaluated with a hyperinsulinemic glucose clamp. They also underwent metabolic studies to measure the level of oxidative stress in their blood.

Dr. Istfan and his co-authors found evidence, more pronounced in participants with a high body mass index (BMI), that the cells were using electrons from glutathione, a “master antioxidant,” to help store excess carbohydrates as fats. This supported their hypothesis that COF may contribute to metabolic distress by limiting antioxidant synthesis in the body.

Upon analyzing biopsies from the participants, the investigators confirmed that in participants with high BMIs, changes in the fat tissue that occurred during the study represented a form of metabolic stress often seen in insulin resistance and type 2 diabetes.

The researchers demonstrated that insulin, which lowers blood sugar by increasing its uptake by the cells, may contribute to metabolic distress when cells are unprepared to process such a large amount of carbohydrates. When an individual consumes excess carbohydrates, cells break down the molecules and resynthesize them into fats through a “reduction” process that uses electrons. The researchers hypothesized that during fat synthesis, the cells may be “taking electrons away” from other metabolic activities, such as the production of antioxidants, which help protect the body from deterioration.

Processed Food at the Root of the Problem

Dr. Apovian says the study highlights that obesity is a disease—and one that will continue to become more prevalent due to the abundance of sugar-laden processed food available today. She adds that as the National Institute of Diabetes and Digestive and Kidney Diseases’ Kevin D. Hall, PhD, showed, processed food is designed to taste good without creating a feeling of being full. It’s a dangerous combination.

“Some people appear to have a genetic predisposition to store more fat in response to COF. In today’s environment, that can easily lead to obesity,” she says. “This is something else we need to prove. But once we can finally show that processed food is a toxin for many people, we can treat it like alcohol, for example.”

According to Dr. Istfan, the methodology used in this study could also be used to examine differences in the efficiency of energy conversion in individuals—and thus their predispositions to weight gain.

“Patients often say they gain weight more easily than other people who eat more than they do. In medicine, we tend to attribute this to the patient’s inability to recall food intake or simply not telling the truth,” he says. “But based on my clinical experience, sometimes the energy conversion is actually different—the patient is gaining weight that we cannot explain just by the calories. That area of metabolism is very important, and if we can figure it out, then we would be contributing a lot to the field and the understanding of how to treat obesity.”

“‘Is a calorie a calorie?’ Continuing this research could actually answer that question in the negative,” Dr. Apovian concludes. “It depends on the metabolic state of the individual and the hormonal milieu that affects whether or not a calorie is burned or stored.

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