Intranasal Oxytocin Cuts Calorie Consumption in Healthy Men

Miriam E Tucker

March 09, 2015

SAN DIEGO — The so-called "love hormone" oxytocin could turn out even more lovely if it proves to be an effective weight-loss drug.

In a first step, a study found that an intranasal formulation of oxytocin cut food consumption by an average of 122 kcal in a single-meal test involving 25 healthy men of varying body mass indexes (BMIs). The results were reported March 8 here at the annual meeting of the Endocrine Society, ENDO 2015, by Elizabeth A Lawson, MD, from Massachusetts General Hospital and Harvard Medical School, Boston.

"This study suggests that oxytocin may reduce the amount of food that people eat and improve the way that the body handles blood sugar. It will be important to do more studies to find out whether we could use oxytocin to treat obesity and [type 2] diabetes," Dr Lawson told Medscape Medical News.

Oxytocin, a hormone produced in the brain, is available in the United States as an intravenous drug for the induction of labor. The synthetic intranasal version used in this study is on the market in Europe, to induce lactation, but is not available in the United States.

In animal studies, oxytocin has been shown to reduce food intake and produce weight loss — presumably through effects on appetite pathways in the brain — as well as increase energy expenditure and improve handling of blood glucose. A small trial of intranasal oxytocin over 8 weeks in humans resulted in weight loss, but mechanisms were not studied, Dr Lawson said.

Session moderator Daniel H Bessesen, MD, from the University of Colorado, Denver, who was not involved in the study, told Medscape Medical News, "For anything to go from an idea to a product is a long, long road. There are definitely animal data to suggest oxytocin affects appetite, but I think most people would not consider it to be a central hormone in appetite regulation. Its main functions are in reproduction. But that doesn't mean it wouldn't have a role. So, I think it's a good thing to study and this…is a very first step."

Interestingly, oxytocin has also been reported to be of benefit in the eating disorder anorexia nervosa, as well as in other psychiatric disorders.

Men Ate Less

The randomized, double-blind, placebo-controlled crossover study used a single dose of 24-IU intranasal oxytocin (Syntocinon, Novartis) in 13 normal-weight (BMI 18.5–24.9 kg/m2) and 12 overweight or obese (BMI 25–40 kg/m2) men aged 18 to 45 years.

"We decided to start with men only because fluctuating hormone levels in women could affect the response to oxytocin. It will be important to study women to determine whether oxytocin has similar effects on food intake and metabolism," Dr Lawson explained.

The subjects were asked to track food intake for 72 hours prior to their first visit and to eat the same foods in the days leading up to the second visit. They came for study visits in the morning after fasting for 12 hours. Food intake leading up to the visits didn't differ among the subjects.

After receiving either oxytocin or placebo, the men selected breakfast from a menu and were offered double portions. Caloric content was calculated, and resting energy expenditure and respiratory quotient (use of carbohydrates and fats as fuel) were assessed. Fasting appetite and appetite-regulating hormones were measured before and after oxytocin or placebo.

While oxytocin didn't affect the number of calories ordered from the menu, it did decrease the total caloric intake by 122 kcal and fat intake by 8.7 g. The effect didn't differ by BMI status, Dr Lawson noted.

There were no significant differences in intake of protein or carbohydrates, in measures of appetite, or in levels of the appetite-regulating hormones leptin, ghrelin, or peptide tyrosine-tyrosine (PYY). Resting energy expenditure also didn't change with oxytocin administration.

Oxytocin resulted in a shift in fuel source to provide energy to the body, decreased carbohydrate utilization, and increased fat utilization. It reduced insulin levels and Homeostatic Model Assessment of Insulin Resistance but had no effect on glucose levels, indicating an improvement in insulin sensitivity among the nondiabetic study subjects, Dr Lawson said.

Oxytocin did not affect blood pressure or heart rate. There were few adverse events in the study. Dizziness, drowsiness, nasal irritation, and abdominal pain were seen, but none were severe, and these did not differ between oxytocin and placebo.

Sustained Over Time?

Dr Lawson pointed out that if the effect of oxytocin is equivalent over three meals per day and sustained over time, the finding of a decrease in food intake of 122 kcal/meal translates to 366 kcal/day, which is about 4 kg over 12 weeks, or more than 17 kg over a year.

By contrast, current Food and Drug Administration (FDA)-approved medications for obesity lead to approximately a 3- to 9-kg weight loss at 1 year.

And, she told Medscape Medical News, the intranasal spray used 3 times a day would cost only about $275/month based on the current cost of the spray in the European Union.

But Dr Bessesen said that the "sustained over time" part is a big question mark. "This was a single-meal test. Weight is regulated over long periods of time….As the weight starts to fall, the body responds to that….There are adaptive responses. When we eat less, we get hungry. The idea that a caloric deficit over a single meal would persist at that level for a year is unrealistic."

However, he said, "The design is good: a randomized, controlled crossover trial. The fact that they find that effect suggests that there's something real here.…Here's a medicine that has been tried in humans before and doesn't seem to have a lot of side effects.…I think it's an interesting first observation."

In response to a reporter's question about other positive effects that have recently been attributed to oxytocin, Dr Lawson said, "It's a hot hormone right now. It has social effects, improves social interactions, increases trust, and improves accurate perception of social cues. I think these effects are independent of what we're seeing."

But given that oxytocin also appears to improve anxiety and depression, which could also curb eating, she said "I think we really need to do more studies."

The study was funded by the National Institutes of Health, the Boston Nutrition Obesity Research Center, and Massachusetts General Hospital Claflin Distinguished Scholar Award. There was no funding from industry. Dr Lawson and coauthors report no relevant financial relationships. Dr Bessesen runs the data safety and monitoring board for Enteromedics.

ENDO 2015: The Endocrine Society Annual Meeting. Abstract OR40-2, presented on March 8, 2015.

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