New Study: Clues as to How Brain Stimulation Beats Food Cravings

Liam Davenport

May 25, 2018

BARCELONA — A new analysis of blood biomarkers before and after a single session of high-frequency deep transcranial magnetic stimulation (dTMS) in obese individuals offers clues as to how the procedure may help reduce food cravings and thereby lower weight.

As reported by Medscape  Medical News, the researchers previously presented a pilot study that showed repeated high-frequency dTMS was associated with an average weight loss of 4.5 kg and reduced food cravings by 34% after 5 weeks compared with a sham procedure in 16 obese patients. They continued to follow the participants and say the effects were maintained for between 6 and 12 months.

The latest results, presented May 21 at the 20th European Congress of Endocrinology (ECE), suggest that dTMS affects metabolic pathways by modulation of sympathetic activity and the hypothalamic-pituitary-adrenal axis.

"For the first time this study is able to suggest how dTMS could alter food cravings in obese subjects," said Livio Luzi, MD, PhD, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato and University of Milan, Italy, in an ECE press release.

"Given the distressing effects of obesity in patients and socioeconomic burden, it is increasingly urgent to identify new strategies to counteract the current obesity trends. dTMS could present a much safer and cheaper alternative to treat obesity compared with drugs or surgery," he added.

Comparison of High-Frequency, Low-Frequency, and Sham Procedures

Previous studies have shown that dTMS affects the mesolimbic and mesostriatal pathways in the brain through cortical excitability. Consequently, it has been used in neuropsychiatric disorders linked to abnormal cortical excitability and dopaminergic activity, such as addiction, in particular smoking, as well as resistant epilepsy and major depression.

In the current study, Luzi and colleagues recruited 40 patients (29 women) who were obese (average BMI, 36.3 kg/m2) to examine the effect of a single 30-minute dTMS session — high-frequency (18 Hz), low-frequency (1 Hz), or sham stimulation — targeted at the prefrontal cortex and insula bilaterally. They assessed metabolic and neuroendocrine parameters in the blood before and after stimulation.

Following high-frequency dTMS, patients had a significant increase in norepinephrine (noradrenaline) levels, from 5.6 ng/mL to 6.5 ng/mL, or a 18.0% increase (P = .01; P = .05 vs low-frequency dTMS).

Moreover, patients experienced a significant rise in beta-endorphin levels, from 0.338 ng/mL to 0.372 ng/mL, or a 13.9% increase (P = .017; P = .010 vs sham; P = .011 vs low-frequency dTMS).

Patients given high-frequency dTMS also had a 7.0% increase in blood glucose levels (P = .002) and 16.3% decrease in leptin levels (P = .002).

These changes were accompanied by decreases in pituitary hormones, with a 20.7% decrease in thyroid stimulating hormone (P = .001) and a 16.3% decrease in prolactin levels (P < .0001).

In the low-frequency dTMS group, salivary cortisol levels decreased after just one session by 29.4% (P = .015).

The team also found that some blood markers varied by gender, "suggesting male/female differences in how vulnerable patients are to food cravings and their ability to lose weight," noted Luzi.

A Few Reasons Why

Speaking to Medscape Medical News, Luzi said it "makes sense" that beta-endorphin release was altered by dTMS, as it "has been demonstrated in all other forms of addiction, so it's a common mechanism that is involved in any addictive disorder, like food addiction." This, he said, is important "because the beta-endorphin release means the reward pathway is activated and can be modulated directly in vivo in humans."

Currently dTMS is only approved, however, for research in obese individuals with a BMI of 30 to 54 kg/m2.

Luzi nevertheless believes that because "the procedure is safe, repeatable, and once you have the machine, is also relatively inexpensive, in my opinion it could be used even earlier, when the person is only overweight and not yet obese, to prevent obesity."

"But that's another story, that's another study, and it's not our present indication for which we are approved."

Turning to possible explanations for why dTMS has such a long-lasting effect on food cravings and weight, Luzi said it could affect neuroplasticity, thus modifying neuronal connectivity, and may also have an effect on the gut microbiota.

"Obese people have a completely different intestinal environment. What we found is that...5 weeks of treatment with dTMS nearly normalized the gut microbiota," he noted.

"But there might be other explanations that we, at present, do not know. It's still a work in progress."

The authors have reported no relevant financial relationships.

European Congress of Endocrinology 2018. May 21, 2018; Barcelona, Spain. Abstract OC6.2

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