Vagus nerve stimulation is already used to treat a handful of conditions such as epilepsy and depression, but a sweeping new review of more than 660 studies suggests medicine has only scratched the surface of its potential.

The paper, published in Comprehensive Physiology, points to treatments across a wide range of disorders, including neurologic, psychiatric, inflammatory, autoimmune, cardiovascular, respiratory, gastrointestinal, metabolic, and renal. Taken together, the findings reveal a striking insight: Modulating the vagus nerve — the longest cranial nerve — may influence systems throughout the body. But scientists still don’t fully understand why or how to precisely control its effects.

The goal was to bring clarity to an increasingly fragmented field, the researchers said. “Until now, there was no comprehensive review that synthesized the mechanisms and evidence across all of these diseases in one place,” said study author Troy (Yifeng) Bu, PhD, affiliate at the UC San Diego Qualcomm Institute and director of design engineering for InflammaSense, a company developing a patch to record vagus nerve signaling.  

How Vagus Nerve Stimulation Works

The vagus nerve isn’t just any nerve — it’s a central communication highway between brain and body.

“We’re hardwired with vagus nerve input to the brain and every organ,” said study author Imanuel Lerman, MD, physician with UC San Diego Health specializing in pain management and the founder of InflammaSense. Carrying information through a complex network of thousands of sensory fibers, the nerve governs reflexes for key body functions such as breathing and heart rate.

Vagus nerve stimulation alters this signaling by delivering electrical impulses at specific frequencies, often 20 Hz. Its effects ripple across body systems, though exactly how that happens is still being worked out. Research points to shifts in neurotransmitters linked to brain plasticity, changes in metabolic regulation, and reduced inflammation.

That last pathway may be especially important. Inflammation is core to many different diseases, said Lerman.

“The same pathways that modulate inflammation are also expressed in the brain,” Lerman said. “So you can directly impact inflammatory processes within the central nervous system.”

Can Vagus Nerve Stimulation Do It All?

Not necessarily.

While the new review is broad, the quality of evidence varies widely, said Michael Kilgard, PhD, professor of neuroscience at UT Dallas and director of the Texas Biomedical Device Center. (Kilgard was not involved in the study.)

There’s also a major divide in the devices.

While implantable vagus nerve stimulators must meet rigorous standards for FDA approval, transcutaneous devices face a much lower bar. “You don’t actually have to show it does anything in a double-blind placebo-controlled trial,” Kilgard said. “None of the studies that use transcutaneous activation are held to that standard.”

Results seen with one device may not translate to another, and the growing direct-to-consumer market adds another layer of uncertainty.

Some wellness devices claim to “activate” the vagus nerve, but that doesn’t mean much. “Every heartbeat activates the vagus nerve,” Kilgard said. “Being alive activates the vagus nerve.” Separating meaningful therapies from that kind of marketing can be difficult for consumers.

What’s Next for Vagus Nerve Therapy?

Realizing the full potential of vagus nerve stimulation will demand stronger evidence and more advanced technology. “Closed-loop” devices are the next frontier, shifting from fixed settings to real-time adjustments based on a patient’s unique physiology. “The future could hold a treatment paradigm in which you immediately know that this person is going to need drug X plus neuromodulation Y,” Lerman said.

More practical challenges remain. Wires in implantable devices can break over time, requiring additional surgery to replace them. Researchers are continuing to explore new applications, particularly for conditions involving inflammation and brain plasticity.

Multiple sclerosis is a particularly compelling target, considering the treatment’s anti-inflammatory effects and support for neural reorganization, Kilgard said. He also pointed to autism and posttraumatic stress disorder as areas of interest.

For now, experts advise caution, especially when it comes to consumer devices. Wellness products that claim to stimulate the vagus nerve lack strong evidence. For patients considering FDA-approved or cleared devices, clinicians should weigh how they fit alongside standard treatments.

“Standard of care is obviously the standard answer,” Lerman said. “But in the future, I think we will have tools that can help stratify and endotype individuals for specific therapies.”

Bu and Lerman reported being affiliated with InflammaSense. Kilgard reported having a financial interest in MicroTransponder Inc. (now Mobia Medical), which markets vagus nerve stimulation therapy for stroke.