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Intranasal oxytocin holds potential for weight loss, improved insulin sensitivity
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SAN DIEGO — A single intranasal dose of the hypothalamic peptide hormone oxytocin reduces caloric intake and has beneficial metabolic effects in adult men, according to research presented at The Endocrine Society annual meeting.
Whether sustained administration of oxytocin is safe and effective to treat patients with obesity warrants further investigation, according to researchers.
“In healthy normal weight, overweight and obese men, a single dose of intranasal oxytocin reduced caloric intake at a breakfast meal,” Elizabeth A. Lawson, MD, MMSc, Massachusetts General Hospital/Harvard Medical School, Boston, MA, said during a press conference. “Oxytocin did not affect levels of appetite-regulating hormones leptin, ghrelin or peptide YY, or increase resting energy expenditure … Oxytocin increased the use of fat as fuel and improved insulin sensitivity. The safety and tolerability profile was acceptable.”
Elizabeth A. Lawson
In a randomized, double-blind, placebo-controlled crossover study involving 25 healthy men (13 with normal weight and 12 with overweight or obesity; mean age, 27.1 ± 1.5 years), Lawson and colleagues investigated the effect of single-dose administration of intranasal oxytocin (24 IU) on caloric intake, appetite and appetite-regulating hormones, and metabolism.
During visits, the men received oxytocin or placebo in random order, selected breakfast from a menu and were given double portions; recorded food intake in the 72 hours leading up to visits did not differ among patients. The caloric content of the food they consumed at the breakfast meal was then calculated.
The investigators evaluated appetite through visual analogue scales. Fasting blood draws were used to assess appetite-regulating hormones (leptin, ghrelin, peptide YY), insulin and glucose before and after oxytocin and placebo. To measure resting energy expenditure and substrate utilization, indirect calorimetry was conducted.
Oxytocin reduced caloric intake at breakfast by 122 ± 51kcal (P = .03). A reduction in fat consumption also was observed with oxytocin (–8.7 ± 3.8g, P = .03) but lost significance after controlling for multiple comparisons. Weight did not affect results.
Appetite or appetite-regulating hormones did not change with oxytocin, nor did resting energy expenditure, but respiratory quotient was reduced (P = .02). Intranasal oxytocin decreased carbohydrate utilization (P = .03) and increased fat utilization (P = .04).
Average insulin levels decreased during three time points (–1.7 ± 0.8 µU/mL, P = .04), with no effect on glucose levels, indicating increased insulin sensitivity.
Few adverse events were reported, and none were severe; no between-group difference was observed with oxytocin compared with placebo.
“Further research will be important to determine whether oxytocin is safe and effective in treating obesity and its metabolic complications,” Lawson said.
Should the effect of oxytocin be equivalent during three meals per day, and sustained over time, the decrease in food intake would translate to approximately 366 kcal per day, 4 kg during 12 weeks and more than 17 kg during a year.
Current FDA-approved medications for obesity result in approximately 3 kg to 9 kg in weight loss during 1 year, Lawson said.
“Further study will be important to determine whether sustained daily oxytocin treatment increases energy expenditure, as seen in the preclinical studies,” Lawson said. “Study of the effects of oxytocin on glucose homeostasis in patients with type 2 diabetes will also be important.” – by Allegra Tiver
Reference:
Lawson EA. OR40-2. Presented at: The Endocrine Society Annual Meeting; March 5-8, 2015, San Diego.
Disclosure: Lawson reports no relevant financial disclosures.
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Tamara L. Wexler, MD, PhD
Lawson and colleagues describe the effect of a single dose of nasal spray oxytocin on caloric intake in men at one subsequent meal; appetite and related hormones were also measured. The study was randomized, double-blind and placebo-controlled, and looked at both normal-weight and overweight/obese individuals. With 25 participants, the four study groups were small; however, alternate treatments were repeated in the same groups, which provided a crossover comparison. Regardless of baseline weight category, there was a significant decrease in consumption of both overall calories and fat intake after oxytocin.
These findings about oxytocin are interesting for several reasons. There is some evidence that oxytocin, in addition its known effects on neuropsychiatric parameters, some animal studies have suggested there may be an impact on appetite or food intake following oxytocin, and a small clinical study in China reported that patients with overweight and obesity had a significant decrease in weight over 8 weeks with the oxytocin nasal spray.
In the study described in this abstract, it is particularly interesting to note that, while there was a statistically significant decrease in consumption of both overall calories and fat after a single spray of oxytocin, there was no difference in appetite or in measured appetite-regulating hormones between oxytocin and placebo groups. Other studies have hypothesized that the effects of oxytocin in this realm might stem from a central effect on the hypothalamus, which also regulates appetite. The results are promising and suggestive, but further investigation on the length of oxytocin response is needed. There is every reason to be excited about the potential once larger studies are conducted (on women and men), looking at length of response from single or repeat doses, and whether weight loss is sustained over time. It would be also be interesting to explore any link between intake and reported neuropsychiatric effects of oxytocin.
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