Background Heart rate variability has been associated with better outcomes for multiple physical and mental health conditions. One method to increase heart rate variability has been proposed to be through modification of the autonomic nervous system though slow paced breathing periods during the day. Objectives The objectives of this study were to review the current literature for studies that attempted to institute slow paced breathing protocols and then to conduct a pilot trial to compare a slow paced breathing protocol to a normal rate but paced breathing protocol in health volunteers. The outcomes of the trial were within-subject change in heart rate variability and perceived psychological stress. Methods We performed a systematic, keyword driven database search including the following key phrases: paced breathing and treatment, paced breathing and intervention, controlled breathing and treatment, and deep breathing and treatment. Selected papers used slow paced breathing to treat different physical and mental health conditions. For the pilot trial, 22 volunteers were randomized to the slow paced breathing group of 5 breaths per minute (bpm) or to the normal but paced breathing group of 14 bpm. Participants were instructed to practice this breathing rate for 10 mins, twice/day (total of 20 mins). They were evaluated at the study site at enrollment and at 2, 4, 6, 8, 10, 12, 14, 16, and 18 weeks during which they breathed at their assigned rate while wearing a Vivo Metric life-shirt, which automatically records heart and respiratory rate. Participants also completed the Perceived Stress Scale at enrollment and follow-ups. Results We reviewed 284 studies and included 23 studies that addressed slow paced breathing mostly for the treatment of hypertension, chronic heart failure, non-cardiac chest pain, neck pain, seizure disorder, space medicine, depression, hot flashes, COPD, induced inflammation, and stress. Of these, 7 were prospective cohort studies, 8 randomized control trials, and 3 case studies. Most studies reported some benefit from slow paced breathing and recommended a rate of ? 6 bpm. There were no reports of side effects from slow paced breathing, other than in a study of COPD patients where 3 bpm was associated with a drop in oxygen saturation. For the pilot trial, baseline characteristics of heart rate variability were similar for the treatment and control groups. Controlled paced breathing was sub-optimally applied in the treatment group. Paced breathing did not result in significant increases in heart rate variability in the treatment versus control group. Both groups had improvement in stress levels after sixteen weeks as measured by within-subject change on the Perceived Stress Scale. Conclusions and Relevance Preliminary evidence supports the use of slow paced breathing to affect heart rate variability by increasing it to high frequency variability. The pilot trial demonstrated the challenges in applying and maintaining a paced breathing protocol. Suggestions for optimizing a protocol include strict monitoring of breathing tracings during each treatment session so that modifications to the protocol can be made in real time. Heart rate variability was obtained among participants who attained a breathing rate of 6 bpm. Future research should seek to optimize the methodology of slow paced breathing so it can more effectively impact existing physical and mental health and potentially also play a role in primary prevention. ABSTRACT Objectives The primary objectives of this study were to determine if slow paced breathing (SPB) could increase and maintain heart rate variability (HRV) and reduce stress in healthy volunteers in a pilot study. The secondary objective was to compare our methodology to that reported by others investigators. Background Diminished autonomic nervous system (ANS) function is observed in hypertension, cardiovascular diseases, inflammation, depression, pain, hot flashes, seizure disorders and other acute and chronic diseases. One method to measure ANS is to measure HRV. In cardiovascular disorders (i.e. post myocardial infarction and post coronary bypass graft surgery), in neurovascular disorders (i.e. stroke and cognitive impairment), infectious diseases (i.e. sepsis), and connective tissue disorders, HRV has been shown to be a predictor of increased morbidity and mortality.Evidence suggests that various lifestyle changes can improve HRV. The objectives of this study were to determine if paced breathing could increase and maintain HRV, and simultaneously decrease stress as measured at the beginning, during, and at the end of a pilot study of slow paced breathing. Methods A total of 22 volunteers were randomized to the SPB group of 5 bpm or the normal (but paced) group of 14 bpm. Participants were instructed to practice this breathing rate for 10 mins, twice/day (total of 20 mins). They were evaluated at the study site at enrollment and at 2, 4, 6, 8, 10, 12, 14, 16, and 18 weeks during which they breathed at their assigned rate while wearing a Vivo Metric life-shirt, which automatically records heart and respiratory rate. Participants also completed the Perceived Stress Scale at enrollment and follow-ups. Preliminary Results Baseline characteristics of heart rate variability were similar for the treatment and control groups. Controlled paced breathing was sub-optimally applied in the treatment group. Paced breathing did not result in significant increases in HRV in treatment versus control groups. Both groups had improvement in stress levels after sixteen weeks as measured by within-subject change on the Perceived Stress Scale. Relevance This study demonstrates the challenges in applying and maintaining a paced breathing protocol. Suggestions for optimizing a protocol include strict monitoring of breathing tracings during each treatment session so that modifications to the protocol can be made in real time. Heart rate variability was obtained among participants who attained a breathing rate of 6 breaths per minute.