By Dr. Lienna Wilson, Licensed Psychologist | Vagus Vitality
When anxiety, a racing heart, and an unsettled stomach all show up at once, it’s natural to treat them as three separate problems. Regina Karpa, PharmD, sees them differently. A compounding and functional medicine pharmacist with nearly two decades of experience across community, specialty, and compounding pharmacy, she has spent much of her career looking at how medications, hormones, metabolism, and daily habits shape the way the body’s systems talk to one another.
Her advanced education includes fellowship training in functional medicine through the American Academy of Anti-Aging Medicine (A4M). She also serves as Oregon State Chapter Leader for the Functional Medicine Pharmacists Alliance (FMPhA). She recently presented on the vagus nerve and gut-brain-heart communication at the Oregon Association of Naturopathic Physicians (OANP) conference. I asked her how the vagus nerve coordinates these systems, what a pharmacist notices that others might miss, what she’s seeing with GLP-1 therapies, and where people can realistically start. Her answers return to one idea she holds firmly: nothing in the body works in isolation.
From the Pharmacy Counter to Functional Medicine
Dr. Karpa has been a pharmacist since 2007 and spent much of her career in traditional retail and specialty pharmacy. Compounding always appealed to her because of what it makes possible. “Compounding had always interested me because of the opportunity to individualize treatment,” she says.
The turning point came from a podcast. As she explored compounding more seriously, she came across a PCCA episode featuring Dr. Pamela Smith discussing functional medicine and bioidentical hormones. “That conversation really sparked my curiosity and opened the door to a different way of looking at patient care,” she says. She became involved with FMPhA and pursued fellowship training through A4M. “What resonated with me was the opportunity to build on my pharmacy background while developing a deeper understanding of the underlying physiology and how different systems in the body influence one another.”
The vagus nerve became a natural focus. “I’ve always been fascinated by how interconnected the body really is, particularly the relationship between the nervous system, hormones, metabolism, and overall health,” she says. “The vagus nerve is a fascinating example of that interconnectedness.” Preparing her OANP presentation brought many of her professional interests together and reinforced a conviction that runs through all of her work. “Nothing in the body works in isolation.”
A Nerve That Does a Lot of Listening
Most people picture the nervous system as the brain sending orders down to the organs. Dr. Karpa points out that the vagus nerve largely works the other way. “Roughly 80% of vagal nerve fibers are sensory, carrying information from the body toward the brain, while about 20% carry signals in the opposite direction,” she explains. “So the vagus nerve is doing a tremendous amount of listening.” Anatomical research supports this picture: the large majority of vagal fibers are afferent, relaying information from the gut and other organs up to the brainstem (Berthoud & Neuhuber, 2000).
“The gut is constantly sending information about digestion, nutrients, and its internal environment, while the cardiovascular system provides feedback about changes in circulation and blood pressure through several neural pathways,” she says. “The brain integrates this information and helps coordinate the body’s response. It’s a continuous, two-way conversation, and the vagus nerve is an important part of it, but certainly not the only pathway involved.” Hormones, immune signals, metabolism, and other parts of the autonomic nervous system all contribute, she adds.
Where a Symptom Shows Up Isn’t Always Where It Starts
That interconnection helps explain why certain symptoms tend to travel together. “Think about someone experiencing digestive discomfort, a racing heart, and increased anxiety during a period of prolonged stress,” Dr. Karpa says. “These may seem like three separate problems, but some of the same physiological processes can influence all three.” Stress can affect gut motility, cardiovascular responses, and how the brain processes signals from the body, and those effects loop back on one another. “What’s happening in the gut can influence how we feel, just as what’s happening in the brain can affect digestion and heart function.”
Because these symptoms appear in different organ systems, she says, the connections between them are easy to overlook. Her approach is to look upstream. “What is influencing the body’s response in the first place? Is it ongoing stress, disrupted sleep, metabolic changes, medications, or a combination of factors?” she asks. “Where a symptom shows up doesn’t always tell us where the problem begins. Understanding those underlying drivers helps us identify where an intervention may be most meaningful.”
Stress Isn’t Only Emotional
Chronic stress, circadian disruption, gut imbalances, and inflammation can all affect autonomic regulation, but Dr. Karpa is wary of ranking them. “These factors rarely occur in isolation, and which one plays the biggest role really depends on the individual,” she says. For one person, stress and poor sleep may be the main drivers. For another, metabolic or hormonal changes, digestive issues, or inflammation may matter more, and often several are feeding into one another.
She also widens the definition of stress. “Stress isn’t always emotional, either,” she says. “The body also responds to physiological stressors such as blood sugar fluctuations, inadequate nutrition, illness, and underlying health conditions.” And she is careful with labels. All of these can influence autonomic regulation, “although I wouldn’t automatically describe that as low vagal tone. What matters is understanding which factors are placing the greatest demands on the system.”
Her starting point is the fundamentals, viewed through the lens of the individual. How consistent is someone’s sleep and wake schedule? Are they eating enough, staying hydrated, and moving regularly? What do their stress and recovery look like, and could medications, metabolic changes, or digestive symptoms be contributing? “There isn’t one protocol that works for everyone,” she says, “and the goal isn’t to eliminate stress or keep the nervous system in a constant state of relaxation. It’s to support the body’s ability to respond appropriately, adapt, and recover.”
What a Pharmacist Notices
As a pharmacist, Dr. Karpa often sees connections that are easy to miss. “One thing people may not realize is that medications can influence autonomic regulation even when they’re prescribed for something completely different,” she says. Some act on autonomic signaling directly. “Certain over-the-counter antihistamines and sleep aids, such as diphenhydramine, have anticholinergic effects that can contribute to constipation, dry mouth, and changes in heart rate.” And sometimes the issue isn’t a single medication but the combined effect of several.
Other medications work more indirectly. Diuretics can shift fluid volume and electrolyte balance, and beta-blockers can change how the heart responds to physical demands or changes in blood pressure. A meta-analysis of randomized controlled trials found that a range of commonly prescribed medications can increase the risk of orthostatic hypotension, the drop in blood pressure some people feel when they stand up (Bhanu et al., 2021). “A medication doesn’t necessarily have to act directly on the vagus nerve to influence the autonomic picture,” Dr. Karpa says. “It may be changing the physiological environment the nervous system has to respond to.”
She also watches for nutrient and electrolyte changes that build slowly. Long-term metformin use can lower vitamin B12, which matters because B12 deficiency can affect neurological function (Medicines and Healthcare products Regulatory Agency [MHRA], 2022). Proton pump inhibitors taken for acid reflux can occasionally contribute to low magnesium, particularly with prolonged use, and certain diuretics can increase losses of potassium or magnesium (National Institutes of Health Office of Dietary Supplements, n.d.). These shifts don’t necessarily signal a problem with the vagus nerve, she notes, but they can contribute to nervous system or cardiovascular symptoms.
That’s why she looks at the whole regimen, including over-the-counter products and supplements, recent medication changes, and whether monitoring is needed. “To me, medication review isn’t just about identifying side effects,” she says. “It’s about understanding how the entire regimen may be shaping the patient’s physiology and where adjustments, when appropriate, could make a meaningful difference.”
Hormones, Thyroid, and Metabolism
“Hormones, metabolism, and the autonomic nervous system are closely interconnected, and changes in one can influence how the others function,” Dr. Karpa says. Thyroid health is a clear example, since thyroid hormones influence metabolic rate, cardiovascular function, and gut motility. “When thyroid hormone levels are elevated, someone may experience palpitations, increased heart rate, anxiety-like symptoms, or digestive changes,” she explains. “When they’re too low, fatigue, constipation, and reduced exercise tolerance may become more noticeable.”
Perimenopause and menopause can also affect temperature regulation, sleep, and cardiovascular responses, and blood sugar adds another layer. “When blood glucose drops too low, the body activates counterregulatory responses that can produce shakiness, sweating, palpitations, or feelings that resemble anxiety,” she says. “That’s why I think it’s important to consider the hormonal and metabolic environment when evaluating symptoms that may appear to be related to the nervous system.”
GLP-1 Therapies and the Gut-Brain Conversation
GLP-1 medications are a vivid example of how closely the gut and brain communicate. Signaling along the gut-brain axis, including vagal pathways, helps regulate appetite and glucose metabolism, and GLP-1 is one of its key messengers (Wachsmuth et al., 2022). “Naturally occurring GLP-1 is released in response to food and helps regulate satiety, gastric emptying, and glucose metabolism,” Dr. Karpa explains. “Semaglutide activates GLP-1 receptors, while tirzepatide activates both GLP-1 and GIP receptors. Both produce longer-lasting effects than naturally occurring GLP-1.”
Those effects can bring substantial benefits for weight management and metabolic health, she notes, with cardiovascular benefits also demonstrated in certain patient populations. “But the same physiological effects that contribute to those benefits can also create trade-offs.” Nausea, vomiting, diarrhea, constipation, and uncomfortable fullness are common. If eating or drinking drops off, or digestive losses are significant, hydration becomes a real concern, and some therapies can modestly raise resting heart rate.
For Dr. Karpa, this is why careful dosing matters. “Appropriate dosing and gradual titration are so important,” she says. “It’s not simply about increasing the dose, but about evaluating treatment response, gastrointestinal tolerance, nutritional intake, and how the individual is responding overall. For me, the goal is to achieve meaningful therapeutic benefits while minimizing adverse effects and supporting the patient’s overall physiology.”
One Simple Practice to Start This Week
Asked which lifestyle strategy makes the biggest difference, Dr. Karpa resists a single answer. “It really depends on what’s placing the greatest demands on the body,” she says. For someone with an irregular schedule, steadier sleep may matter most. For someone else, nutrition, digestive symptoms, or metabolic health may be the priority. “Every time we eat, we’re sending hormonal, metabolic, and neural signals throughout the body,” she notes. Regular movement builds the body’s capacity to respond to physical demands and recover, and with gut-focused therapies, she prefers to understand what’s actually happening before introducing targeted interventions. “Often, it’s the consistent attention to these fundamentals, rather than complicated protocols, that can make the most meaningful difference.”
If she had to pick one practice to begin this week, it would be slow-paced breathing. “Even five minutes a day can be a good starting point,” she says. “For example, gently inhaling for about four seconds and exhaling for six brings the breathing rate to approximately six breaths per minute.” A systematic review and meta-analysis found that voluntary slow breathing increases vagally mediated heart rate variability during practice (Laborde et al., 2022).
Box breathing, with four phases of inhaling, holding, exhaling, and holding again, often for four seconds each, is another option. “What matters is finding a rhythm that feels comfortable rather than forcing a particular technique,” she says. She is also clear about what these practices are and aren’t. “I see these practices as supportive tools, not a quick fix or a way to permanently increase vagal tone. What I like is that they’re accessible, can be adapted to the individual, and don’t require complicated protocols.”
Supplements, Devices, and Choosing for the Right Reasons
Before recommending any supplement, device, or compounded therapy, Dr. Karpa wants to know what it’s meant to address. “Have we identified the underlying contributors? Is there a clear clinical reason for introducing another intervention?” she asks. “I believe these therapies can have an important place, but they should build on a solid foundation rather than replace it.”
Among supplements, she notes that magnesium may help when intake or magnesium status is a concern, omega-3 fatty acids may have a role in certain cardiovascular or metabolic conditions, and melatonin may help when sleep timing or circadian rhythm is disrupted. “These aren’t necessarily direct vagus nerve interventions,” she says. “Their value depends on the individual’s needs, and we still have to consider appropriate dosing, potential interactions, and safety.”
With vagus nerve stimulation, she draws a clear line between established treatments and emerging technology. Implanted stimulators have approved uses for certain neurological and psychiatric conditions, and some prescription noninvasive devices are used for specific headache disorders. “Auricular stimulation, which targets nerve branches in the outer ear, is another interesting area of research,” she says, “although the evidence and treatment protocols for broader applications are still evolving. These approaches aren’t interchangeable, and not every device marketed for vagus nerve stimulation has the same level of evidence behind it.”
The same thinking applies to compounding and peptides. “As a compounding pharmacist, I appreciate the important role compounding plays in individualized patient care, particularly when commercially available medications cannot adequately meet a patient’s needs,” she says. “But whether we’re discussing compounded therapies, supplements, or emerging peptides, I believe it’s important to understand the clinical purpose, what the available evidence supports, and where uncertainties remain.”
With so many products sold online, quality and sourcing matter. For supplements, she looks for reputable manufacturers, transparent labeling, and independent quality testing whenever it’s available. Prescription therapies, she adds, should involve appropriate medical oversight and properly licensed pharmacies. “To me, personalized care isn’t about adding the newest supplement, device, or therapy,” she says. “It’s about understanding the individual, choosing interventions for the right reasons, and making sure they’re supported by evidence, quality, and safety.”
The Whole Picture
Across every topic, Dr. Karpa returns to the idea that first drew her to functional medicine. The gut, brain, and heart are in constant conversation, and medications, hormones, metabolism, sleep, and stress all shape what they say to one another. Supporting the vagus nerve, in her view, is less about any single tool and more about understanding the whole person, and then starting with the simplest step that fits.
About Regina Karpa, PharmD
Dr. Karpa is a compounding and functional medicine pharmacist with nearly two decades of experience across community, specialty, and compounding pharmacy. She earned her Doctor of Pharmacy degree from the University of Southern California in 2007. Her advanced education includes fellowship training in functional medicine through the American Academy of Anti-Aging Medicine (A4M). She also serves as the Oregon State Chapter Leader for the Functional Medicine Pharmacists Alliance (FMPhA).
Her professional interests include hormone and metabolic health, individualized therapies, and understanding how medications, lifestyle, and physiology influence overall health. At the heart of her approach is the understanding that nothing in the body works in isolation. Find out more at: https://www.linkedin.com/in/regina-karpa-pharmd-06653b19/.
Medical Disclaimer: This article is for educational purposes only and is not a substitute for individualized medical advice. Please don’t start, stop, or change any medication or supplement without first talking with your healthcare provider. GLP-1 therapies, compounded therapies, and vagus nerve stimulation devices should be used only under appropriate medical supervision.
References
Berthoud, H.-R., & Neuhuber, W. L. (2000). Functional and chemical anatomy of the afferent vagal system. Autonomic Neuroscience, 85(1–3), 1–17. https://doi.org/10.1016/S1566-0702(00)00215-0
Bhanu, C., Nimmons, D., Petersen, I., Orlu, M., Davis, D., Hussain, H., Magammanage, S., & Walters, K. (2021). Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials. PLOS Medicine, 18(11), e1003821. https://doi.org/10.1371/journal.pmed.1003821
Laborde, S., Allen, M. S., Borges, U., Dosseville, F., Hosang, T. J., Iskra, M., Mosley, E., Salvotti, C., Spolverato, L., Zammit, N., & Javelle, F. (2022). Effects of voluntary slow breathing on heart rate and heart rate variability: A systematic review and a meta-analysis. Neuroscience & Biobehavioral Reviews, 138, 104711. https://doi.org/10.1016/j.neubiorev.2022.104711
Medicines and Healthcare products Regulatory Agency. (2022). Metformin and reduced vitamin B12 levels: New advice for monitoring patients at risk. Drug Safety Update. https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk
National Institutes of Health Office of Dietary Supplements. (n.d.). Magnesium: Fact sheet for health professionals. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/
Wachsmuth, H. R., Weninger, S. N., & Duca, F. A. (2022). Role of the gut–brain axis in energy and glucose metabolism. Experimental & Molecular Medicine, 54(4), 377–392. https://doi.org/10.1038/s12276-021-00677-w