Endoscopic Sleeve Gastroplasty is an Effective Treatment for Obesity in a Veteran With Metabolic and Psychiatric Comorbidities

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Endoscopic Sleeve Gastroplasty is an Effective Treatment for Obesity in a Veteran With Metabolic and Psychiatric Comorbidities

Obesity is a growing worldwide epidemic with significant implications for individual health and public health care costs. It is also associated with several medical conditions, including diabetes, cardiovascular disease, cancer, and mental health disorders.1 Comprehensive lifestyle intervention is a first-line therapy for obesity consisting of dietary and exercise interventions. Despite initial success, long-term results and durability of weight loss with lifestyle modifications are limited. 2 Bariatric surgery, including sleeve gastrectomy and gastric bypass surgery, is a more invasive approach that is highly effective in weight loss. However, these operations are not reversible, and patients may not be eligible for or may not desire surgery. Overall, bariatric surgery is widely underutilized, with < 1% of eligible patients ultimately undergoing surgery.3,4

Endoscopic bariatric therapies are increasingly popular procedures that address the need for additional treatments for obesity among individuals who have not had success with lifestyle changes and are not surgical candidates. The most common procedure is the endoscopic sleeve gastroplasty (ESG), which applies full-thickness sutures in the stomach to reduce gastric volume, delay gastric emptying, and limit food intake while keeping the fundus intact compared with sleeve gastrectomy. This procedure is typically considered in patients with body mass index (BMI) ≥ 30, who do not qualify for or do not want traditional bariatric surgery. The literature supports robust outcomes after ESG, with studies demonstrating significant and sustained total body weight loss of up to 14% to 16% at 5 years and significant improvement in ≥ 1 metabolic comorbidities in 80% of patients.5,6 ESG adverse events (AEs) include abdominal pain, nausea, and vomiting that are typically self-limited to 1 week. Rarer but more serious AEs include bleeding, perforation, or infection, and occur in 2% of cases based on large trial data.5,7

Although the weight loss benefits of ESG are well established, to date, there are limited data on the effects of endoscopic bariatric therapies like ESG on mental health conditions. Here, we describe a case of a veteran with a history of mental health disorders that prevented him from completing bariatric surgery. The patient underwent ESG and had a successful clinical course.

CASE PRESENTATION

A 59-year-old male veteran with a medical history of class III obesity (42.4 BMI), obstructive sleep apnea, hypothyroidism, hypertension, type 2 diabetes mellitus, and a large ventral hernia was referred to the MOVE! (Management of Overweight/ Obese Veterans Everywhere!) multidisciplinary high-intensity weight loss program at the US Department of Veterans Affairs (VA) West Los Angeles VA Medical Center (WLAVAMC). His psychiatric history included generalized anxiety disorder, posttraumatic stress disorder (PTSD), and panic disorder, managed by the Psychiatry Service and treated with sertraline 25 mg daily, lorazepam 0.5 mg twice daily, and hydroxyzine 20 mg nightly. He had previously implemented lifestyle changes and attended MOVE! classes and nutrition coaching for 1 year but was unsuccessful in losing weight. He had also tried liraglutide 3 mg daily for weight loss but was unable to tolerate it and reported worsening medication-related anxiety.

The patient declined further weight loss pharmacotherapy and was referred to bariatric surgery. He was scheduled for a surgical sleeve gastrectomy. However, on the day he arrived at the hospital for surgery, he developed severe anxiety and had a panic attack, and it was canceled. Due to his mental health issues, he was no longer comfortable proceeding with surgery and was left without other options for obesity treatment. The veteran was extremely disappointed because the ventral hernia caused significant quality of life impairment, limited his ability to exercise, and caused him embarrassment in public settings. The hernia could not be surgically repaired until there was significant weight loss.

A bariatric endoscopy program within the Division of Gastroenterology was developed and implemented at the WLAVAMC in February 2023 in conjunction with MOVE! The patient was referred for consideration of an endoscopic weight loss procedure. He was determined to be a suitable candidate for ESG based on his BMI being > 40 and personal preference not to proceed with surgery to lose enough weight to qualify for hernia repair. The veteran underwent an endoscopy, which showed normal anatomy and gastric mucosa. ESG was performed in standard fashion (Figure).8 Three vertical lines were made using argon plasma coagulation from the incisura to 2 cm below the gastroesophageal junction along the anterior, posterior, and greater curvature of the stomach to mark the area for endoscopic suture placement. Starting at the incisura, 7 full-thickness sutures were placed to create a volume reduction plication, with preservation of the fundus. The patient did well postprocedure with no immediate or delayed AEs and was discharged home the same day.

FDP042062_F1

 

Follow-up

The veteran followed a gradual dietary advancement from a clear liquid diet to pureed and soft texture food. The patient’s weight dropped from 359 lbs preprocedure to 304 lbs 6 months postprocedure, a total body weight loss (TWBL) of 15.3%. At 12 months the veteran weighed 299 lbs (16.7% TBWL). He also had notable improvements in metabolic parameters. His systolic blood pressure decreased from ≥ 140 mm Hg to 120 to 130 mm Hg and hemoglobin A1c dropped from 7.0% to 6.3%. Remarkably, his psychiatrist noted significant improvement in his overall mental health. The veteran reported complete cessation of panic attacks since the ESG, improvements in PTSD and anxiety, and was able to discontinue lorazepam and decrease his dose of sertraline to 12.5 mg daily. He reported feeling more energetic and goal-oriented with increased clarity of thought. Perhaps the most significant outcome was that after the 55-lb weight loss at 6 months, the patient was eligible to undergo ventral hernia surgical repair, which had previously contributed to shame and social isolation. This, in turn, improved his quality of life, allowed him to start walking again, up to 8 miles daily, and to feel comfortable again going out in public settings.

DISCUSSION

Bariatric surgeries are an effective method of achieving weight loss and improving obesity-related comorbidities. However, only a small percentage of individuals with obesity are candidates for bariatric surgery. Given the dramatic increase in the prevalence of obesity, other options are needed. Specifically, within the VA, an estimated 80% of veterans are overweight or obese, but only about 500 bariatric surgeries are performed annually.9 With the need for additional weight loss therapies, VA programs are starting to offer endoscopic bariatric procedures as an alternative option. This may be a desirable choice for patients with obesity (BMI > 30), with or without associated metabolic comorbidities, who need more aggressive intervention beyond dietary and lifestyle changes and are either not interested in or not eligible for bariatric surgery or weight loss medications.

Although there is evidence that metabolic comorbidities are associated with obesity, there has been less research on obesity and mental health comorbidities such as depression and anxiety. These psychiatric conditions may even be more common among patients seeking weight loss procedures and more prominent in certain groups such as veterans, which may ultimately exclude these patients from bariatric surgery.10 Prior studies suggest that bariatric surgery can reduce the severity of depression and, to a lesser extent, anxiety symptoms at 2 years following the initial surgery; however, there is limited literature describing the impact of weight loss procedure on panic disorders.11-14 We suspect that a weight loss procedure such as ESG may have indirectly improved the veteran’s mood disorder due to the weight loss it induced, increasing the ability to exercise, quality of sleep, and participation in public settings.

This case highlights a veteran who did not tolerate weight loss medication and had severe anxiety and PTSD that prevented him from going through with bariatric surgery. He then underwent an endoscopic weight loss procedure. The ESG helped him successfully achieve significant weight loss, increase his physical activity, reduce his anxiety and panic disorder, and overall, significantly improve his quality of life. More than 1 year after the procedure, the patient has sustained improvements in his psychiatric and emotional health along with durable weight loss, maintaining > 15% of his total weight lost. Additional studies are needed to further understand the prevalence and long-term outcomes of mental health comorbidities, as well as weight loss outcomes in this group of patients who undergo endoscopic bariatric procedures.

CONCLUSIONS

We describe a case of a veteran with severe obesity and significant psychiatric comorbidities that prevented him from undergoing bariatric surgery, who underwent an ESG. This procedure led to significant weight loss, improvement of metabolic parameters, reduction in anxiety and PTSD, and enhancement of his quality of life. This case emphasizes the unique advantages of ESG and supports the expansion of endoscopic bariatric programs in the VA.

References
  1. Ritchie SA, Connell JM. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007;17(4):319-326. doi:10.1016/j.numecd.2006.07.005
  2. Bray GA, Kim KK, Wilding JPH; World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-723. doi:10.1111/obr.12551
  3. Imbus JR, Voils CI, Funk LM. Bariatric surgery barriers: a review using andersen’s model of health services use. Surg Obes Relat Dis. 2018;14(3):404-412. doi:10.1016/j.soard.2017.11.012
  4. Dawes AJ, Maggard-Gibbons M, Maher AR, et al. Mental health conditions among patients seeking and undergoing bariatric surgery: a meta-analysis. JAMA. 2016;315(2):150- 163. doi:10.1001/jama.2015.18118
  5. Abu Dayyeh BK, Bazerbachi F, Vargas EJ, et al.. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022;400(10350):441-451. doi:10.1016/S0140-6736(22)01280-6
  6. Matteo MV, Bove V, Ciasca G, et al. Success predictors of endoscopic sleeve gastroplasty. Obes Surg. 2024;34(5):1496-1504. doi:10.1007/s11695-024-07109-4
  7. Maselli DB, Hoff AC, Kucera A, et al. Endoscopic sleeve gastroplasty in class III obesity: efficacy, safety, and durability outcomes in 404 consecutive patients. World J Gastrointest Endosc. 2023;15(6):469-479. doi:10.4253/wjge.v15.i6.469
  8. Kumar N, Abu Dayyeh BK, Lopez-Nava Breviere G, et al. Endoscopic sutured gastroplasty: procedure evolution from first-in-man cases through current technique. Surg Endosc. 2018;32(4):2159-2164. doi:10.1007/s00464-017-5869-2
  9. Maggard-Gibbons M, Shekelle PG, Girgis MD, et al. Endoscopic Bariatric Interventions versus lifestyle interventions or surgery for weight loss in patients with obesity: a systematic review and meta-analysis. Department of Veterans Affairs (US); 2022. https://www.ncbi.nlm.nih.gov/books/NBK587943/
  10. Maggard Gibbons MA, Maher AM, Dawes AJ, et al. Psychological clearance for bariatric surgery: a systematic review. VA-ESP project #05-2262014.
  11. van Hout GC, Verschure SK, van Heck GL. Psychosocial predictors of success following bariatric surgery. Obes Surg. 2005;15(4):552-560. doi:10.1381/0960892053723484
  12. Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the national comorbidity survey replication. Biol Psychiatry. 2007;61(3):348-358. doi:10.1016/j.biopsych.2006.03.040
  13. Aylward L, Lilly C, Konsor M, et al. How soon do depression and anxiety symptoms improve after bariatric surgery?. Healthcare (Basel). 2023;11(6):862. doi:10.3390/healthcare11060862
  14. Law S, Dong S, Zhou F, Zheng D, Wang C, Dong Z. Bariatric surgery and mental health outcomes: an umbrella review. Front Endocrinol (Lausanne). 2023;14:1283621. doi:10.3389/fendo.2023.1283621
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Philip Kozan, MDa; Mehran Kashefi, DOa,b; Maria Romanova, MDa,b; Jennifer M. Kolb, MD, MSa,b

Author affiliations:
aDavid Geffen School of Medicine at University of California Los Angeles
bVeterans Affairs Greater Los Angeles Health Care System, California

Author disclosures: Jennifer Kolb is a consultant for Castle Biosciences. The other authors report no actual or potential conflicts of interest with regard to this article.

Correspondence: Philip Kozan ([email protected])

Fed Pract. 2025;42(1). Published online January 17. doi:10.12788/fp.0546

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Philip Kozan, MDa; Mehran Kashefi, DOa,b; Maria Romanova, MDa,b; Jennifer M. Kolb, MD, MSa,b

Author affiliations:
aDavid Geffen School of Medicine at University of California Los Angeles
bVeterans Affairs Greater Los Angeles Health Care System, California

Author disclosures: Jennifer Kolb is a consultant for Castle Biosciences. The other authors report no actual or potential conflicts of interest with regard to this article.

Correspondence: Philip Kozan ([email protected])

Fed Pract. 2025;42(1). Published online January 17. doi:10.12788/fp.0546

Author and Disclosure Information

Philip Kozan, MDa; Mehran Kashefi, DOa,b; Maria Romanova, MDa,b; Jennifer M. Kolb, MD, MSa,b

Author affiliations:
aDavid Geffen School of Medicine at University of California Los Angeles
bVeterans Affairs Greater Los Angeles Health Care System, California

Author disclosures: Jennifer Kolb is a consultant for Castle Biosciences. The other authors report no actual or potential conflicts of interest with regard to this article.

Correspondence: Philip Kozan ([email protected])

Fed Pract. 2025;42(1). Published online January 17. doi:10.12788/fp.0546

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Article PDF

Obesity is a growing worldwide epidemic with significant implications for individual health and public health care costs. It is also associated with several medical conditions, including diabetes, cardiovascular disease, cancer, and mental health disorders.1 Comprehensive lifestyle intervention is a first-line therapy for obesity consisting of dietary and exercise interventions. Despite initial success, long-term results and durability of weight loss with lifestyle modifications are limited. 2 Bariatric surgery, including sleeve gastrectomy and gastric bypass surgery, is a more invasive approach that is highly effective in weight loss. However, these operations are not reversible, and patients may not be eligible for or may not desire surgery. Overall, bariatric surgery is widely underutilized, with < 1% of eligible patients ultimately undergoing surgery.3,4

Endoscopic bariatric therapies are increasingly popular procedures that address the need for additional treatments for obesity among individuals who have not had success with lifestyle changes and are not surgical candidates. The most common procedure is the endoscopic sleeve gastroplasty (ESG), which applies full-thickness sutures in the stomach to reduce gastric volume, delay gastric emptying, and limit food intake while keeping the fundus intact compared with sleeve gastrectomy. This procedure is typically considered in patients with body mass index (BMI) ≥ 30, who do not qualify for or do not want traditional bariatric surgery. The literature supports robust outcomes after ESG, with studies demonstrating significant and sustained total body weight loss of up to 14% to 16% at 5 years and significant improvement in ≥ 1 metabolic comorbidities in 80% of patients.5,6 ESG adverse events (AEs) include abdominal pain, nausea, and vomiting that are typically self-limited to 1 week. Rarer but more serious AEs include bleeding, perforation, or infection, and occur in 2% of cases based on large trial data.5,7

Although the weight loss benefits of ESG are well established, to date, there are limited data on the effects of endoscopic bariatric therapies like ESG on mental health conditions. Here, we describe a case of a veteran with a history of mental health disorders that prevented him from completing bariatric surgery. The patient underwent ESG and had a successful clinical course.

CASE PRESENTATION

A 59-year-old male veteran with a medical history of class III obesity (42.4 BMI), obstructive sleep apnea, hypothyroidism, hypertension, type 2 diabetes mellitus, and a large ventral hernia was referred to the MOVE! (Management of Overweight/ Obese Veterans Everywhere!) multidisciplinary high-intensity weight loss program at the US Department of Veterans Affairs (VA) West Los Angeles VA Medical Center (WLAVAMC). His psychiatric history included generalized anxiety disorder, posttraumatic stress disorder (PTSD), and panic disorder, managed by the Psychiatry Service and treated with sertraline 25 mg daily, lorazepam 0.5 mg twice daily, and hydroxyzine 20 mg nightly. He had previously implemented lifestyle changes and attended MOVE! classes and nutrition coaching for 1 year but was unsuccessful in losing weight. He had also tried liraglutide 3 mg daily for weight loss but was unable to tolerate it and reported worsening medication-related anxiety.

The patient declined further weight loss pharmacotherapy and was referred to bariatric surgery. He was scheduled for a surgical sleeve gastrectomy. However, on the day he arrived at the hospital for surgery, he developed severe anxiety and had a panic attack, and it was canceled. Due to his mental health issues, he was no longer comfortable proceeding with surgery and was left without other options for obesity treatment. The veteran was extremely disappointed because the ventral hernia caused significant quality of life impairment, limited his ability to exercise, and caused him embarrassment in public settings. The hernia could not be surgically repaired until there was significant weight loss.

A bariatric endoscopy program within the Division of Gastroenterology was developed and implemented at the WLAVAMC in February 2023 in conjunction with MOVE! The patient was referred for consideration of an endoscopic weight loss procedure. He was determined to be a suitable candidate for ESG based on his BMI being > 40 and personal preference not to proceed with surgery to lose enough weight to qualify for hernia repair. The veteran underwent an endoscopy, which showed normal anatomy and gastric mucosa. ESG was performed in standard fashion (Figure).8 Three vertical lines were made using argon plasma coagulation from the incisura to 2 cm below the gastroesophageal junction along the anterior, posterior, and greater curvature of the stomach to mark the area for endoscopic suture placement. Starting at the incisura, 7 full-thickness sutures were placed to create a volume reduction plication, with preservation of the fundus. The patient did well postprocedure with no immediate or delayed AEs and was discharged home the same day.

FDP042062_F1

 

Follow-up

The veteran followed a gradual dietary advancement from a clear liquid diet to pureed and soft texture food. The patient’s weight dropped from 359 lbs preprocedure to 304 lbs 6 months postprocedure, a total body weight loss (TWBL) of 15.3%. At 12 months the veteran weighed 299 lbs (16.7% TBWL). He also had notable improvements in metabolic parameters. His systolic blood pressure decreased from ≥ 140 mm Hg to 120 to 130 mm Hg and hemoglobin A1c dropped from 7.0% to 6.3%. Remarkably, his psychiatrist noted significant improvement in his overall mental health. The veteran reported complete cessation of panic attacks since the ESG, improvements in PTSD and anxiety, and was able to discontinue lorazepam and decrease his dose of sertraline to 12.5 mg daily. He reported feeling more energetic and goal-oriented with increased clarity of thought. Perhaps the most significant outcome was that after the 55-lb weight loss at 6 months, the patient was eligible to undergo ventral hernia surgical repair, which had previously contributed to shame and social isolation. This, in turn, improved his quality of life, allowed him to start walking again, up to 8 miles daily, and to feel comfortable again going out in public settings.

DISCUSSION

Bariatric surgeries are an effective method of achieving weight loss and improving obesity-related comorbidities. However, only a small percentage of individuals with obesity are candidates for bariatric surgery. Given the dramatic increase in the prevalence of obesity, other options are needed. Specifically, within the VA, an estimated 80% of veterans are overweight or obese, but only about 500 bariatric surgeries are performed annually.9 With the need for additional weight loss therapies, VA programs are starting to offer endoscopic bariatric procedures as an alternative option. This may be a desirable choice for patients with obesity (BMI > 30), with or without associated metabolic comorbidities, who need more aggressive intervention beyond dietary and lifestyle changes and are either not interested in or not eligible for bariatric surgery or weight loss medications.

Although there is evidence that metabolic comorbidities are associated with obesity, there has been less research on obesity and mental health comorbidities such as depression and anxiety. These psychiatric conditions may even be more common among patients seeking weight loss procedures and more prominent in certain groups such as veterans, which may ultimately exclude these patients from bariatric surgery.10 Prior studies suggest that bariatric surgery can reduce the severity of depression and, to a lesser extent, anxiety symptoms at 2 years following the initial surgery; however, there is limited literature describing the impact of weight loss procedure on panic disorders.11-14 We suspect that a weight loss procedure such as ESG may have indirectly improved the veteran’s mood disorder due to the weight loss it induced, increasing the ability to exercise, quality of sleep, and participation in public settings.

This case highlights a veteran who did not tolerate weight loss medication and had severe anxiety and PTSD that prevented him from going through with bariatric surgery. He then underwent an endoscopic weight loss procedure. The ESG helped him successfully achieve significant weight loss, increase his physical activity, reduce his anxiety and panic disorder, and overall, significantly improve his quality of life. More than 1 year after the procedure, the patient has sustained improvements in his psychiatric and emotional health along with durable weight loss, maintaining > 15% of his total weight lost. Additional studies are needed to further understand the prevalence and long-term outcomes of mental health comorbidities, as well as weight loss outcomes in this group of patients who undergo endoscopic bariatric procedures.

CONCLUSIONS

We describe a case of a veteran with severe obesity and significant psychiatric comorbidities that prevented him from undergoing bariatric surgery, who underwent an ESG. This procedure led to significant weight loss, improvement of metabolic parameters, reduction in anxiety and PTSD, and enhancement of his quality of life. This case emphasizes the unique advantages of ESG and supports the expansion of endoscopic bariatric programs in the VA.

Obesity is a growing worldwide epidemic with significant implications for individual health and public health care costs. It is also associated with several medical conditions, including diabetes, cardiovascular disease, cancer, and mental health disorders.1 Comprehensive lifestyle intervention is a first-line therapy for obesity consisting of dietary and exercise interventions. Despite initial success, long-term results and durability of weight loss with lifestyle modifications are limited. 2 Bariatric surgery, including sleeve gastrectomy and gastric bypass surgery, is a more invasive approach that is highly effective in weight loss. However, these operations are not reversible, and patients may not be eligible for or may not desire surgery. Overall, bariatric surgery is widely underutilized, with < 1% of eligible patients ultimately undergoing surgery.3,4

Endoscopic bariatric therapies are increasingly popular procedures that address the need for additional treatments for obesity among individuals who have not had success with lifestyle changes and are not surgical candidates. The most common procedure is the endoscopic sleeve gastroplasty (ESG), which applies full-thickness sutures in the stomach to reduce gastric volume, delay gastric emptying, and limit food intake while keeping the fundus intact compared with sleeve gastrectomy. This procedure is typically considered in patients with body mass index (BMI) ≥ 30, who do not qualify for or do not want traditional bariatric surgery. The literature supports robust outcomes after ESG, with studies demonstrating significant and sustained total body weight loss of up to 14% to 16% at 5 years and significant improvement in ≥ 1 metabolic comorbidities in 80% of patients.5,6 ESG adverse events (AEs) include abdominal pain, nausea, and vomiting that are typically self-limited to 1 week. Rarer but more serious AEs include bleeding, perforation, or infection, and occur in 2% of cases based on large trial data.5,7

Although the weight loss benefits of ESG are well established, to date, there are limited data on the effects of endoscopic bariatric therapies like ESG on mental health conditions. Here, we describe a case of a veteran with a history of mental health disorders that prevented him from completing bariatric surgery. The patient underwent ESG and had a successful clinical course.

CASE PRESENTATION

A 59-year-old male veteran with a medical history of class III obesity (42.4 BMI), obstructive sleep apnea, hypothyroidism, hypertension, type 2 diabetes mellitus, and a large ventral hernia was referred to the MOVE! (Management of Overweight/ Obese Veterans Everywhere!) multidisciplinary high-intensity weight loss program at the US Department of Veterans Affairs (VA) West Los Angeles VA Medical Center (WLAVAMC). His psychiatric history included generalized anxiety disorder, posttraumatic stress disorder (PTSD), and panic disorder, managed by the Psychiatry Service and treated with sertraline 25 mg daily, lorazepam 0.5 mg twice daily, and hydroxyzine 20 mg nightly. He had previously implemented lifestyle changes and attended MOVE! classes and nutrition coaching for 1 year but was unsuccessful in losing weight. He had also tried liraglutide 3 mg daily for weight loss but was unable to tolerate it and reported worsening medication-related anxiety.

The patient declined further weight loss pharmacotherapy and was referred to bariatric surgery. He was scheduled for a surgical sleeve gastrectomy. However, on the day he arrived at the hospital for surgery, he developed severe anxiety and had a panic attack, and it was canceled. Due to his mental health issues, he was no longer comfortable proceeding with surgery and was left without other options for obesity treatment. The veteran was extremely disappointed because the ventral hernia caused significant quality of life impairment, limited his ability to exercise, and caused him embarrassment in public settings. The hernia could not be surgically repaired until there was significant weight loss.

A bariatric endoscopy program within the Division of Gastroenterology was developed and implemented at the WLAVAMC in February 2023 in conjunction with MOVE! The patient was referred for consideration of an endoscopic weight loss procedure. He was determined to be a suitable candidate for ESG based on his BMI being > 40 and personal preference not to proceed with surgery to lose enough weight to qualify for hernia repair. The veteran underwent an endoscopy, which showed normal anatomy and gastric mucosa. ESG was performed in standard fashion (Figure).8 Three vertical lines were made using argon plasma coagulation from the incisura to 2 cm below the gastroesophageal junction along the anterior, posterior, and greater curvature of the stomach to mark the area for endoscopic suture placement. Starting at the incisura, 7 full-thickness sutures were placed to create a volume reduction plication, with preservation of the fundus. The patient did well postprocedure with no immediate or delayed AEs and was discharged home the same day.

FDP042062_F1

 

Follow-up

The veteran followed a gradual dietary advancement from a clear liquid diet to pureed and soft texture food. The patient’s weight dropped from 359 lbs preprocedure to 304 lbs 6 months postprocedure, a total body weight loss (TWBL) of 15.3%. At 12 months the veteran weighed 299 lbs (16.7% TBWL). He also had notable improvements in metabolic parameters. His systolic blood pressure decreased from ≥ 140 mm Hg to 120 to 130 mm Hg and hemoglobin A1c dropped from 7.0% to 6.3%. Remarkably, his psychiatrist noted significant improvement in his overall mental health. The veteran reported complete cessation of panic attacks since the ESG, improvements in PTSD and anxiety, and was able to discontinue lorazepam and decrease his dose of sertraline to 12.5 mg daily. He reported feeling more energetic and goal-oriented with increased clarity of thought. Perhaps the most significant outcome was that after the 55-lb weight loss at 6 months, the patient was eligible to undergo ventral hernia surgical repair, which had previously contributed to shame and social isolation. This, in turn, improved his quality of life, allowed him to start walking again, up to 8 miles daily, and to feel comfortable again going out in public settings.

DISCUSSION

Bariatric surgeries are an effective method of achieving weight loss and improving obesity-related comorbidities. However, only a small percentage of individuals with obesity are candidates for bariatric surgery. Given the dramatic increase in the prevalence of obesity, other options are needed. Specifically, within the VA, an estimated 80% of veterans are overweight or obese, but only about 500 bariatric surgeries are performed annually.9 With the need for additional weight loss therapies, VA programs are starting to offer endoscopic bariatric procedures as an alternative option. This may be a desirable choice for patients with obesity (BMI > 30), with or without associated metabolic comorbidities, who need more aggressive intervention beyond dietary and lifestyle changes and are either not interested in or not eligible for bariatric surgery or weight loss medications.

Although there is evidence that metabolic comorbidities are associated with obesity, there has been less research on obesity and mental health comorbidities such as depression and anxiety. These psychiatric conditions may even be more common among patients seeking weight loss procedures and more prominent in certain groups such as veterans, which may ultimately exclude these patients from bariatric surgery.10 Prior studies suggest that bariatric surgery can reduce the severity of depression and, to a lesser extent, anxiety symptoms at 2 years following the initial surgery; however, there is limited literature describing the impact of weight loss procedure on panic disorders.11-14 We suspect that a weight loss procedure such as ESG may have indirectly improved the veteran’s mood disorder due to the weight loss it induced, increasing the ability to exercise, quality of sleep, and participation in public settings.

This case highlights a veteran who did not tolerate weight loss medication and had severe anxiety and PTSD that prevented him from going through with bariatric surgery. He then underwent an endoscopic weight loss procedure. The ESG helped him successfully achieve significant weight loss, increase his physical activity, reduce his anxiety and panic disorder, and overall, significantly improve his quality of life. More than 1 year after the procedure, the patient has sustained improvements in his psychiatric and emotional health along with durable weight loss, maintaining > 15% of his total weight lost. Additional studies are needed to further understand the prevalence and long-term outcomes of mental health comorbidities, as well as weight loss outcomes in this group of patients who undergo endoscopic bariatric procedures.

CONCLUSIONS

We describe a case of a veteran with severe obesity and significant psychiatric comorbidities that prevented him from undergoing bariatric surgery, who underwent an ESG. This procedure led to significant weight loss, improvement of metabolic parameters, reduction in anxiety and PTSD, and enhancement of his quality of life. This case emphasizes the unique advantages of ESG and supports the expansion of endoscopic bariatric programs in the VA.

References
  1. Ritchie SA, Connell JM. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007;17(4):319-326. doi:10.1016/j.numecd.2006.07.005
  2. Bray GA, Kim KK, Wilding JPH; World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-723. doi:10.1111/obr.12551
  3. Imbus JR, Voils CI, Funk LM. Bariatric surgery barriers: a review using andersen’s model of health services use. Surg Obes Relat Dis. 2018;14(3):404-412. doi:10.1016/j.soard.2017.11.012
  4. Dawes AJ, Maggard-Gibbons M, Maher AR, et al. Mental health conditions among patients seeking and undergoing bariatric surgery: a meta-analysis. JAMA. 2016;315(2):150- 163. doi:10.1001/jama.2015.18118
  5. Abu Dayyeh BK, Bazerbachi F, Vargas EJ, et al.. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022;400(10350):441-451. doi:10.1016/S0140-6736(22)01280-6
  6. Matteo MV, Bove V, Ciasca G, et al. Success predictors of endoscopic sleeve gastroplasty. Obes Surg. 2024;34(5):1496-1504. doi:10.1007/s11695-024-07109-4
  7. Maselli DB, Hoff AC, Kucera A, et al. Endoscopic sleeve gastroplasty in class III obesity: efficacy, safety, and durability outcomes in 404 consecutive patients. World J Gastrointest Endosc. 2023;15(6):469-479. doi:10.4253/wjge.v15.i6.469
  8. Kumar N, Abu Dayyeh BK, Lopez-Nava Breviere G, et al. Endoscopic sutured gastroplasty: procedure evolution from first-in-man cases through current technique. Surg Endosc. 2018;32(4):2159-2164. doi:10.1007/s00464-017-5869-2
  9. Maggard-Gibbons M, Shekelle PG, Girgis MD, et al. Endoscopic Bariatric Interventions versus lifestyle interventions or surgery for weight loss in patients with obesity: a systematic review and meta-analysis. Department of Veterans Affairs (US); 2022. https://www.ncbi.nlm.nih.gov/books/NBK587943/
  10. Maggard Gibbons MA, Maher AM, Dawes AJ, et al. Psychological clearance for bariatric surgery: a systematic review. VA-ESP project #05-2262014.
  11. van Hout GC, Verschure SK, van Heck GL. Psychosocial predictors of success following bariatric surgery. Obes Surg. 2005;15(4):552-560. doi:10.1381/0960892053723484
  12. Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the national comorbidity survey replication. Biol Psychiatry. 2007;61(3):348-358. doi:10.1016/j.biopsych.2006.03.040
  13. Aylward L, Lilly C, Konsor M, et al. How soon do depression and anxiety symptoms improve after bariatric surgery?. Healthcare (Basel). 2023;11(6):862. doi:10.3390/healthcare11060862
  14. Law S, Dong S, Zhou F, Zheng D, Wang C, Dong Z. Bariatric surgery and mental health outcomes: an umbrella review. Front Endocrinol (Lausanne). 2023;14:1283621. doi:10.3389/fendo.2023.1283621
References
  1. Ritchie SA, Connell JM. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007;17(4):319-326. doi:10.1016/j.numecd.2006.07.005
  2. Bray GA, Kim KK, Wilding JPH; World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-723. doi:10.1111/obr.12551
  3. Imbus JR, Voils CI, Funk LM. Bariatric surgery barriers: a review using andersen’s model of health services use. Surg Obes Relat Dis. 2018;14(3):404-412. doi:10.1016/j.soard.2017.11.012
  4. Dawes AJ, Maggard-Gibbons M, Maher AR, et al. Mental health conditions among patients seeking and undergoing bariatric surgery: a meta-analysis. JAMA. 2016;315(2):150- 163. doi:10.1001/jama.2015.18118
  5. Abu Dayyeh BK, Bazerbachi F, Vargas EJ, et al.. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022;400(10350):441-451. doi:10.1016/S0140-6736(22)01280-6
  6. Matteo MV, Bove V, Ciasca G, et al. Success predictors of endoscopic sleeve gastroplasty. Obes Surg. 2024;34(5):1496-1504. doi:10.1007/s11695-024-07109-4
  7. Maselli DB, Hoff AC, Kucera A, et al. Endoscopic sleeve gastroplasty in class III obesity: efficacy, safety, and durability outcomes in 404 consecutive patients. World J Gastrointest Endosc. 2023;15(6):469-479. doi:10.4253/wjge.v15.i6.469
  8. Kumar N, Abu Dayyeh BK, Lopez-Nava Breviere G, et al. Endoscopic sutured gastroplasty: procedure evolution from first-in-man cases through current technique. Surg Endosc. 2018;32(4):2159-2164. doi:10.1007/s00464-017-5869-2
  9. Maggard-Gibbons M, Shekelle PG, Girgis MD, et al. Endoscopic Bariatric Interventions versus lifestyle interventions or surgery for weight loss in patients with obesity: a systematic review and meta-analysis. Department of Veterans Affairs (US); 2022. https://www.ncbi.nlm.nih.gov/books/NBK587943/
  10. Maggard Gibbons MA, Maher AM, Dawes AJ, et al. Psychological clearance for bariatric surgery: a systematic review. VA-ESP project #05-2262014.
  11. van Hout GC, Verschure SK, van Heck GL. Psychosocial predictors of success following bariatric surgery. Obes Surg. 2005;15(4):552-560. doi:10.1381/0960892053723484
  12. Hudson JI, Hiripi E, Pope HG Jr, Kessler RC. The prevalence and correlates of eating disorders in the national comorbidity survey replication. Biol Psychiatry. 2007;61(3):348-358. doi:10.1016/j.biopsych.2006.03.040
  13. Aylward L, Lilly C, Konsor M, et al. How soon do depression and anxiety symptoms improve after bariatric surgery?. Healthcare (Basel). 2023;11(6):862. doi:10.3390/healthcare11060862
  14. Law S, Dong S, Zhou F, Zheng D, Wang C, Dong Z. Bariatric surgery and mental health outcomes: an umbrella review. Front Endocrinol (Lausanne). 2023;14:1283621. doi:10.3389/fendo.2023.1283621
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The Gut Microbiome and Cardiac Arrhythmias

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The Gut Microbiome and Cardiac Arrhythmias

The extensive surface of the gastrointestinal tract presents an interface between the human body and its environment. Residing within the intestinal lumen, ingested food and various microorganisms are an essential aspect of this relationship. The trillions of microorganisms, primarily commensal bacteria hosted by the human gut, constitute the human gut microbiome.

There is growing evidence that the human gut microbiome plays a role in maintaining normal body function and homeostasis.1 Research, such as the National Institute of Health Microbiome Project, is helping to show the impact of gut microorganisms and their negative influence on metabolic diseases and chronic inflammatory disorders.2-5 An imbalance in the microbiota, known as dysbiosis, has been associated with metabolic and cardiovascular diseases (CVD), including hypertension, diabetes mellitus, obesity, and coronary artery disease (CAD). Gut dysbiosis has also been associated with cardiac arrhythmias, including atrial fibrillation (AF) and ventricular arrhythmias (Figure).6-12

FDP04207264_F1

Whether gut dysbiosis is a cause or effect of the human disease process is unclear. While further research is warranted, some evidence of causation has been found. In 2018, Yoshida et al demonstrated an association between patients with CAD who had a significantly lower burden of the gut bacteria species Bacteroides vulgatus and Bacteroides dorei compared to that of patients without CAD. The study found that administration of these Bacteroides species reduced atherosclerotic lesion formation in atherosclerosis-prone mice.13 If altering gut microbial composition can affect the disease process, it may indicate a causative role for gut dysbiosis in disease pathogenesis. Furthermore, this finding also suggests agents may be used to alter the gut microbiome and potentially prevent and treat diseases. An altered gut microbiome may serve as an early marker for human disease, aiding in timely diagnosis and institution of disease-modifying treatments.

This review outlines the broad relationship of the pathways and intermediaries that may be involved in mediating the interaction between the gut microbiome and cardiac arrhythmias based on rapidly increasing evidence. A comprehensive search among PubMed and Google Scholar databases was conducted to find articles relevant to the topic.

Potential Intermediaries

Potential pathways for how the gut microbiome and cardiovascular system interact are subjects of active research. However, recent research may point to potential mechanisms of the association between the systems. The gut microbiome may influence human physiology through 3 principal routes: the autonomic nervous system, inflammatory pathways, and metabolic processes.

Autonomic Nervous System

The concept of bidirectional communication between the gut and central nervous system, known as the microbiota-gut-brain axis, is widely accepted.14 Proposed mediators of this interaction include the vagus nerve, the sympathetic nervous system, and the hypothalamic-pituitary-adrenal axis; cytokines produced by the immune system, tryptophan metabolism, and the production of short-chain fatty acids (SCFAs).15,16

The gut microbiome appears to have a direct impact on the autonomic nervous system, through which it can influence cardiovascular function. Muller et al described how the gut microbiome modulated gut-extrinsic sympathetic neurons and that the depletion of gut microbiota led to activation of both brainstem sensory nuclei and efferent sympathetic premotor glutamatergic neurons.16 Meng et al found that systemic injection of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) led to significantly increased activity in the paraventricular nucleus, a hypothalamic structure essential to the central autonomic network. Their study demonstrated that systemic TMAO also led to increased left stellate ganglion (LSG) activity, a known contributor to cardiac sympathetic tone.12

Inflammatory Pathways

Inflammatory responses are another pathway for the gut microbiome to influence the cardiovascular system. SCFAs are a set of gut microbial metabolites produced in the colon by bacterial fermentation and decomposition of resistant starches and dietary fibers.17 These metabolites are increasingly recognized for their role in modulating disease processes, including cardiac disease. Aguilar et al found that the progression of atherosclerosis was slowed in apolipoprotein E (Apo-E) knockout mice by a chow diet supplemented with butyrate, a SCFA, suggesting it is an atheroprotective therapeutic agent. Less adhesion and migration of macrophages, reduced inflammation, improved plaque stability, and lowered atherosclerosis progression.18 Wei et al demonstrated in animal models that direct microinjection of the proinflammatory factors interleukin (IL)-1Β and tumor necrosis factor (TNF)-αdirectly into the subfornical organ increased heart rate, mean blood pressure, and renal sympathetic nerve activity.19

Metabolic Processes

Serotonin (5-HT), a metabolite of tryptophan, is a neurotransmitter that regulates many bodily functions and plays a significant role in the microbiota-brain gut axis.20 Oral ingestion of the bacterial species Bifidobacterium infantis increased plasma tryptophan in rat models.21 Additionally, many other microorganisms, including species of Candida, Streptococcus, Escherichia, and Enterococcus are known to produce 5-HT.22 While a relationship between the gut microbiome and plasma 5-HT has been established, interactions between 5-HT and the cardiovascular system are complex. Research has shown that stimulation of 5-HT1A receptors produces bradycardic and vasopressor effects, while stimulation of the 5-HT2 receptor induces vasoconstriction and tachycardia.23

A high-fiber diet can lower the incidence of hypertension, although the mechanisms are not clear. One potential reason could be alteration in gut bacteria, as a diet high in fiber has been shown to increase the prevalence of acetate-producing bacteria.24

Atherosclerosis

Research investigating the relationship of the gut microbiome with arrhythmias is in its early stages; however, the connection of the gut microbiome and atherosclerosis is more established.25 Contemporary studies have shown various gut microorganisms associated with atherosclerosis.26 Jie et al reported that patients with atherosclerotic cardiovascular disease had increased Enterobacteriaceae loads and oral cavity-associated bacteria with lower levels of butyrate producing bacteria when compared with healthy controls.27 In addition, microbial metabolites such as TMAO appear to promote atherosclerosis by increasing vascular inflammation and platelet reactivity.26 Researchers are investigating the modulation of these associations to help reduce atherosclerotic burden. Kasahara et al found that Roseburia intestinalis could reduce atherosclerotic disease in mice through the production of butyrate.28 Roberts et al established that administration of TMAO inhibitors reduced TMAO levels while reducing thrombus formation without observable toxicity or increased bleeding risk.29

Atrial Arrhythmias

The gut microbiome can also specifically affect cardiac arrhythmogenesis, and multiple studies suggest possible mediators of this interaction. Certain gut microbiome derived metabolites like TMAO may have a role in promoting AF.30 Other gut microbial metabolites like lipopolysaccharides and indoxyl sulfate are implicated in atrial electrical instability.31,32 Microbe-derived free fatty acids such as palmitic acid and adrenic acid can precipitate arrhythmogenesis. 33,34 Preponderances of certain gut bacteria like Ruminococcus, Streptococcus, and Enterococcus, as well as reductions of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila have been detected in patients with AF.8 Tabata et al found that certain clusters of bacterial groups led by Ruminococcus species seem to show higher prevalence in patients with AF, whereas the genus Enterobacter was significantly lower compared with control subjects. That study also noted that gut microbial composition is affected by diet and antacid use.35 Gut microbiome-derived serotonin may be another mediator for AF, which may be related to the fact that 5-HT4 receptors are present in atrial tissue.36

Ventricular Arrhythmias

A critical component to the development of malignant ventricular arrhythmias is an imbalance in autonomic tone; in particular, the overactivation of the sympathetic nervous system.37 Animal models have shown that augmentation of the sympathetic nervous system plays an essential role in the subsequent development of ventricular arrhythmias. 38 Several studies have established the LSG as an important component of the cardiac sympathetic nervous system pathway. 38,39 Ablation of the LSG has been shown to effectively reduce the burden of malignant arrhythmias, further pointing toward the role of excess sympathetic activity.37,39 Stellate ganglion denervation has become an established method for managing life-threatening ventricular arrhythmias.40

Gut metabolites may have significant effects on cardiac sympathetic activity. Meng et al investigated the effect of TMAO on the LSG in animals and its overall effect on the incidence of ventricular arrhythmias under ischemic conditions. To fully explore this interaction, they examined the effect of TMAO on LSG function though 2 mechanisms: local administration of TMAO within the LSG and systemic administration of TMAO leading to activation of the central sympathetic nervous system. In both protocols, left anterior descending coronary artery occlusion was performed after TMAO administration. Injection of TMAO directly into the LSG was found to significantly increase the cardiac sympathetic tone and incidence of ventricular arrhythmias. In the systemic administration control arm, ventricular arrhythmias were also significantly increased.12

Increased inflammatory states appear to correlate with an increase in sympathetic tone and ventricular arrhythmias.12 In an animal study, direct injection of the proinflammatory factor IL-1Β into the LSG not only resulted in increased inflammation, but aggravated cardiac sympathetic remodeling. This led to a decreased effective refractory period and action potential duration, leading to an increased maximal slope of the restitution curve and higher occurrence of ventricular arrhythmias.41 Shi et al demonstrated that paraventricular nucleus microinjection with TNF-α and IL-1Β also enhanced the cardiac sympathetic afferent reflex, showing that these proinflammatory cytokines not only upregulate the inflammatory response, but can also have excitatory effects that stimulate sympathetic activity and have the potential to be proarrhythmic.19,42 Local and systemic administration of the gut microbe-derived TMAO increased the expression of IL-1Β and TNF-α, thus implicating the microbiome as a potential mediator of the inflammatory response and as another potential pathway for increased ventricular arrhythmias.12

The N-methyl-d-aspartate receptor (NMDAR) is found in multiple organs—including the heart—but more specifically in the conducting system and myocardium.43,44 Research has discovered an upregulation of NMDARs in the setting of cardiac sympathetic hyperinnervation in rat models both with healed myocardial necrotic injury and without. The infusion of their ligand, NMDA, provoked ventricular tachycardia and ventricular fibrillation in rat models with sympathetic hyperinnervation and healed myocardial necrotic injury.45 Another study found that NMDAR activation provoked ventricular arrhythmias, but also prolonged repolarization and induced electrical instability.46 Proinflammatory markers have been shown to upregulate the expression of NMDARs; more importantly, NMDAR expression has been shown to be significantly increased in the setting of TMAO administration.12,47,48

5-HT also appears to have a substantial association with ventricular arrhythmias in addition to atrial arrhythmias. el-Mahdy demonstrated in anesthetized rats with acute coronary ligation that systemic doses of 5-HT represented a significant dose-dependent increase in the duration of ventricular tachycardia and ventricular fibrillation, while also increasing the number of ventricular ectopic beats.49 Certain gut microorganisms are known to produce 5-HT, including those in the genera Streptococcus, Escherichia, and Enterococcus.22 Additionally, oral ingestion of the Bifidobacterium infantis increased plasma levels of tryptophan in rat models.21 The gut microbiome may have significant effects on plasma serotonin levels, and thus have the potential to alter the risk for ventricular arrhythmias.

The deleterious effects of the gut microbiome have been documented. However, it appears to have potential protective effects, and several studies point to the possible mechanisms of this beneficial interaction. Propionate is a SCFA microorganism produced by gut microbial fermentation.50 In a rat model study, Zhou et al found that infusion of sodium propionate significantly reduced ventricular arrhythmias during acute myocardial ischemia or burst stimulation, thus confirming cardioprotective effects.50,51

Proposed mechanisms for reduced susceptibility to ventricular arrhythmias with propionate infusion include parasympathetic activation via the gut-brain axis, anti-inflammatory pathways, and improved cardiac electrophysiology instability.50 In addition butyrate has been found to reduce inflammation and myocardial hypertrophy. Jiang et al demonstrated in rats postmyocardial infarction that butyrate promoted expression of anti-inflammatory M2 macrophage markers, decreased expressions of nerve growth factor and norepinephrine, and decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase. The cumulative impact of butyrate led to suppression of inflammation and the inhibition of sympathetic neural remodeling, ultimately resulting in improved cardiac function and reduction in ventricular arrhythmias after myocardial infarction.52

Gut bacteria-derived acetate-mediated reduction in cardiac fibrosis may be another mechanism for the effects on ventricular arrhythmias. Cardiac fibrosis and scar are established as the primary substrate for reentrant ventricular arrhythmias seen in various cardiomyopathies.

Future Directions

The microbiome residing in the human gut has a significant impact on cardiac arrhythmias, the details of which remain unknown. A likely bidirectional relationship exists in which the gut microbiome may affect arrhythmogenesis and in turn be affected by cardiac arrhythmias. The mechanisms of action are not well understood, but likely involve the autonomic nervous system, inflammation, and metabolic pathways.

The gut microbiome is a complex collection of heterogenous microorganisms that have dramatic effects on the human body. Additional research is necessary to identify further associations and causations of gut microorganisms with various human body processes, as well as cardiovascular disease. The microbiome has been shown to directly and indirectly influence the development of different disease states, including the cardiovascular system and cardiac arrhythmias. Several pathways have been proposed through which the gut microbiome can potentially affect cardiac arrhythmogenesis. There are likely several mechanisms simultaneously in operation. Understanding the role of human gut microbiome in the genesis of cardiac arrhythmias not only may improve our understanding of arrhythmias, but also may result in novel treatment options. This could potentially lead to the development of therapeutic options and strategies to modulate the gut microbiome to help detect, prevent, and treat cardiac arrhythmias.

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bMalcolm Randall Veterans Affairs Medical Center, Gainesville, Florida

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Correspondence: Ramil Goel ([email protected])

Fed Pract. 2025;42(7). Published online July 17. doi:10.12788/fp.0595

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Richard A. Vautier, MDa; Elaine M. Sumners, PhDa; Mohan K. Raizada, PhDa; Carl J. Pepine, MD, MACCa; Ramil Goel, MD, FHRSa,b

Author affiliations
aUniversity of Florida, Gainesville
bMalcolm Randall Veterans Affairs Medical Center, Gainesville, Florida

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article

Correspondence: Ramil Goel ([email protected])

Fed Pract. 2025;42(7). Published online July 17. doi:10.12788/fp.0595

Author and Disclosure Information

Richard A. Vautier, MDa; Elaine M. Sumners, PhDa; Mohan K. Raizada, PhDa; Carl J. Pepine, MD, MACCa; Ramil Goel, MD, FHRSa,b

Author affiliations
aUniversity of Florida, Gainesville
bMalcolm Randall Veterans Affairs Medical Center, Gainesville, Florida

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article

Correspondence: Ramil Goel ([email protected])

Fed Pract. 2025;42(7). Published online July 17. doi:10.12788/fp.0595

Article PDF
Article PDF

The extensive surface of the gastrointestinal tract presents an interface between the human body and its environment. Residing within the intestinal lumen, ingested food and various microorganisms are an essential aspect of this relationship. The trillions of microorganisms, primarily commensal bacteria hosted by the human gut, constitute the human gut microbiome.

There is growing evidence that the human gut microbiome plays a role in maintaining normal body function and homeostasis.1 Research, such as the National Institute of Health Microbiome Project, is helping to show the impact of gut microorganisms and their negative influence on metabolic diseases and chronic inflammatory disorders.2-5 An imbalance in the microbiota, known as dysbiosis, has been associated with metabolic and cardiovascular diseases (CVD), including hypertension, diabetes mellitus, obesity, and coronary artery disease (CAD). Gut dysbiosis has also been associated with cardiac arrhythmias, including atrial fibrillation (AF) and ventricular arrhythmias (Figure).6-12

FDP04207264_F1

Whether gut dysbiosis is a cause or effect of the human disease process is unclear. While further research is warranted, some evidence of causation has been found. In 2018, Yoshida et al demonstrated an association between patients with CAD who had a significantly lower burden of the gut bacteria species Bacteroides vulgatus and Bacteroides dorei compared to that of patients without CAD. The study found that administration of these Bacteroides species reduced atherosclerotic lesion formation in atherosclerosis-prone mice.13 If altering gut microbial composition can affect the disease process, it may indicate a causative role for gut dysbiosis in disease pathogenesis. Furthermore, this finding also suggests agents may be used to alter the gut microbiome and potentially prevent and treat diseases. An altered gut microbiome may serve as an early marker for human disease, aiding in timely diagnosis and institution of disease-modifying treatments.

This review outlines the broad relationship of the pathways and intermediaries that may be involved in mediating the interaction between the gut microbiome and cardiac arrhythmias based on rapidly increasing evidence. A comprehensive search among PubMed and Google Scholar databases was conducted to find articles relevant to the topic.

Potential Intermediaries

Potential pathways for how the gut microbiome and cardiovascular system interact are subjects of active research. However, recent research may point to potential mechanisms of the association between the systems. The gut microbiome may influence human physiology through 3 principal routes: the autonomic nervous system, inflammatory pathways, and metabolic processes.

Autonomic Nervous System

The concept of bidirectional communication between the gut and central nervous system, known as the microbiota-gut-brain axis, is widely accepted.14 Proposed mediators of this interaction include the vagus nerve, the sympathetic nervous system, and the hypothalamic-pituitary-adrenal axis; cytokines produced by the immune system, tryptophan metabolism, and the production of short-chain fatty acids (SCFAs).15,16

The gut microbiome appears to have a direct impact on the autonomic nervous system, through which it can influence cardiovascular function. Muller et al described how the gut microbiome modulated gut-extrinsic sympathetic neurons and that the depletion of gut microbiota led to activation of both brainstem sensory nuclei and efferent sympathetic premotor glutamatergic neurons.16 Meng et al found that systemic injection of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) led to significantly increased activity in the paraventricular nucleus, a hypothalamic structure essential to the central autonomic network. Their study demonstrated that systemic TMAO also led to increased left stellate ganglion (LSG) activity, a known contributor to cardiac sympathetic tone.12

Inflammatory Pathways

Inflammatory responses are another pathway for the gut microbiome to influence the cardiovascular system. SCFAs are a set of gut microbial metabolites produced in the colon by bacterial fermentation and decomposition of resistant starches and dietary fibers.17 These metabolites are increasingly recognized for their role in modulating disease processes, including cardiac disease. Aguilar et al found that the progression of atherosclerosis was slowed in apolipoprotein E (Apo-E) knockout mice by a chow diet supplemented with butyrate, a SCFA, suggesting it is an atheroprotective therapeutic agent. Less adhesion and migration of macrophages, reduced inflammation, improved plaque stability, and lowered atherosclerosis progression.18 Wei et al demonstrated in animal models that direct microinjection of the proinflammatory factors interleukin (IL)-1Β and tumor necrosis factor (TNF)-αdirectly into the subfornical organ increased heart rate, mean blood pressure, and renal sympathetic nerve activity.19

Metabolic Processes

Serotonin (5-HT), a metabolite of tryptophan, is a neurotransmitter that regulates many bodily functions and plays a significant role in the microbiota-brain gut axis.20 Oral ingestion of the bacterial species Bifidobacterium infantis increased plasma tryptophan in rat models.21 Additionally, many other microorganisms, including species of Candida, Streptococcus, Escherichia, and Enterococcus are known to produce 5-HT.22 While a relationship between the gut microbiome and plasma 5-HT has been established, interactions between 5-HT and the cardiovascular system are complex. Research has shown that stimulation of 5-HT1A receptors produces bradycardic and vasopressor effects, while stimulation of the 5-HT2 receptor induces vasoconstriction and tachycardia.23

A high-fiber diet can lower the incidence of hypertension, although the mechanisms are not clear. One potential reason could be alteration in gut bacteria, as a diet high in fiber has been shown to increase the prevalence of acetate-producing bacteria.24

Atherosclerosis

Research investigating the relationship of the gut microbiome with arrhythmias is in its early stages; however, the connection of the gut microbiome and atherosclerosis is more established.25 Contemporary studies have shown various gut microorganisms associated with atherosclerosis.26 Jie et al reported that patients with atherosclerotic cardiovascular disease had increased Enterobacteriaceae loads and oral cavity-associated bacteria with lower levels of butyrate producing bacteria when compared with healthy controls.27 In addition, microbial metabolites such as TMAO appear to promote atherosclerosis by increasing vascular inflammation and platelet reactivity.26 Researchers are investigating the modulation of these associations to help reduce atherosclerotic burden. Kasahara et al found that Roseburia intestinalis could reduce atherosclerotic disease in mice through the production of butyrate.28 Roberts et al established that administration of TMAO inhibitors reduced TMAO levels while reducing thrombus formation without observable toxicity or increased bleeding risk.29

Atrial Arrhythmias

The gut microbiome can also specifically affect cardiac arrhythmogenesis, and multiple studies suggest possible mediators of this interaction. Certain gut microbiome derived metabolites like TMAO may have a role in promoting AF.30 Other gut microbial metabolites like lipopolysaccharides and indoxyl sulfate are implicated in atrial electrical instability.31,32 Microbe-derived free fatty acids such as palmitic acid and adrenic acid can precipitate arrhythmogenesis. 33,34 Preponderances of certain gut bacteria like Ruminococcus, Streptococcus, and Enterococcus, as well as reductions of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila have been detected in patients with AF.8 Tabata et al found that certain clusters of bacterial groups led by Ruminococcus species seem to show higher prevalence in patients with AF, whereas the genus Enterobacter was significantly lower compared with control subjects. That study also noted that gut microbial composition is affected by diet and antacid use.35 Gut microbiome-derived serotonin may be another mediator for AF, which may be related to the fact that 5-HT4 receptors are present in atrial tissue.36

Ventricular Arrhythmias

A critical component to the development of malignant ventricular arrhythmias is an imbalance in autonomic tone; in particular, the overactivation of the sympathetic nervous system.37 Animal models have shown that augmentation of the sympathetic nervous system plays an essential role in the subsequent development of ventricular arrhythmias. 38 Several studies have established the LSG as an important component of the cardiac sympathetic nervous system pathway. 38,39 Ablation of the LSG has been shown to effectively reduce the burden of malignant arrhythmias, further pointing toward the role of excess sympathetic activity.37,39 Stellate ganglion denervation has become an established method for managing life-threatening ventricular arrhythmias.40

Gut metabolites may have significant effects on cardiac sympathetic activity. Meng et al investigated the effect of TMAO on the LSG in animals and its overall effect on the incidence of ventricular arrhythmias under ischemic conditions. To fully explore this interaction, they examined the effect of TMAO on LSG function though 2 mechanisms: local administration of TMAO within the LSG and systemic administration of TMAO leading to activation of the central sympathetic nervous system. In both protocols, left anterior descending coronary artery occlusion was performed after TMAO administration. Injection of TMAO directly into the LSG was found to significantly increase the cardiac sympathetic tone and incidence of ventricular arrhythmias. In the systemic administration control arm, ventricular arrhythmias were also significantly increased.12

Increased inflammatory states appear to correlate with an increase in sympathetic tone and ventricular arrhythmias.12 In an animal study, direct injection of the proinflammatory factor IL-1Β into the LSG not only resulted in increased inflammation, but aggravated cardiac sympathetic remodeling. This led to a decreased effective refractory period and action potential duration, leading to an increased maximal slope of the restitution curve and higher occurrence of ventricular arrhythmias.41 Shi et al demonstrated that paraventricular nucleus microinjection with TNF-α and IL-1Β also enhanced the cardiac sympathetic afferent reflex, showing that these proinflammatory cytokines not only upregulate the inflammatory response, but can also have excitatory effects that stimulate sympathetic activity and have the potential to be proarrhythmic.19,42 Local and systemic administration of the gut microbe-derived TMAO increased the expression of IL-1Β and TNF-α, thus implicating the microbiome as a potential mediator of the inflammatory response and as another potential pathway for increased ventricular arrhythmias.12

The N-methyl-d-aspartate receptor (NMDAR) is found in multiple organs—including the heart—but more specifically in the conducting system and myocardium.43,44 Research has discovered an upregulation of NMDARs in the setting of cardiac sympathetic hyperinnervation in rat models both with healed myocardial necrotic injury and without. The infusion of their ligand, NMDA, provoked ventricular tachycardia and ventricular fibrillation in rat models with sympathetic hyperinnervation and healed myocardial necrotic injury.45 Another study found that NMDAR activation provoked ventricular arrhythmias, but also prolonged repolarization and induced electrical instability.46 Proinflammatory markers have been shown to upregulate the expression of NMDARs; more importantly, NMDAR expression has been shown to be significantly increased in the setting of TMAO administration.12,47,48

5-HT also appears to have a substantial association with ventricular arrhythmias in addition to atrial arrhythmias. el-Mahdy demonstrated in anesthetized rats with acute coronary ligation that systemic doses of 5-HT represented a significant dose-dependent increase in the duration of ventricular tachycardia and ventricular fibrillation, while also increasing the number of ventricular ectopic beats.49 Certain gut microorganisms are known to produce 5-HT, including those in the genera Streptococcus, Escherichia, and Enterococcus.22 Additionally, oral ingestion of the Bifidobacterium infantis increased plasma levels of tryptophan in rat models.21 The gut microbiome may have significant effects on plasma serotonin levels, and thus have the potential to alter the risk for ventricular arrhythmias.

The deleterious effects of the gut microbiome have been documented. However, it appears to have potential protective effects, and several studies point to the possible mechanisms of this beneficial interaction. Propionate is a SCFA microorganism produced by gut microbial fermentation.50 In a rat model study, Zhou et al found that infusion of sodium propionate significantly reduced ventricular arrhythmias during acute myocardial ischemia or burst stimulation, thus confirming cardioprotective effects.50,51

Proposed mechanisms for reduced susceptibility to ventricular arrhythmias with propionate infusion include parasympathetic activation via the gut-brain axis, anti-inflammatory pathways, and improved cardiac electrophysiology instability.50 In addition butyrate has been found to reduce inflammation and myocardial hypertrophy. Jiang et al demonstrated in rats postmyocardial infarction that butyrate promoted expression of anti-inflammatory M2 macrophage markers, decreased expressions of nerve growth factor and norepinephrine, and decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase. The cumulative impact of butyrate led to suppression of inflammation and the inhibition of sympathetic neural remodeling, ultimately resulting in improved cardiac function and reduction in ventricular arrhythmias after myocardial infarction.52

Gut bacteria-derived acetate-mediated reduction in cardiac fibrosis may be another mechanism for the effects on ventricular arrhythmias. Cardiac fibrosis and scar are established as the primary substrate for reentrant ventricular arrhythmias seen in various cardiomyopathies.

Future Directions

The microbiome residing in the human gut has a significant impact on cardiac arrhythmias, the details of which remain unknown. A likely bidirectional relationship exists in which the gut microbiome may affect arrhythmogenesis and in turn be affected by cardiac arrhythmias. The mechanisms of action are not well understood, but likely involve the autonomic nervous system, inflammation, and metabolic pathways.

The gut microbiome is a complex collection of heterogenous microorganisms that have dramatic effects on the human body. Additional research is necessary to identify further associations and causations of gut microorganisms with various human body processes, as well as cardiovascular disease. The microbiome has been shown to directly and indirectly influence the development of different disease states, including the cardiovascular system and cardiac arrhythmias. Several pathways have been proposed through which the gut microbiome can potentially affect cardiac arrhythmogenesis. There are likely several mechanisms simultaneously in operation. Understanding the role of human gut microbiome in the genesis of cardiac arrhythmias not only may improve our understanding of arrhythmias, but also may result in novel treatment options. This could potentially lead to the development of therapeutic options and strategies to modulate the gut microbiome to help detect, prevent, and treat cardiac arrhythmias.

The extensive surface of the gastrointestinal tract presents an interface between the human body and its environment. Residing within the intestinal lumen, ingested food and various microorganisms are an essential aspect of this relationship. The trillions of microorganisms, primarily commensal bacteria hosted by the human gut, constitute the human gut microbiome.

There is growing evidence that the human gut microbiome plays a role in maintaining normal body function and homeostasis.1 Research, such as the National Institute of Health Microbiome Project, is helping to show the impact of gut microorganisms and their negative influence on metabolic diseases and chronic inflammatory disorders.2-5 An imbalance in the microbiota, known as dysbiosis, has been associated with metabolic and cardiovascular diseases (CVD), including hypertension, diabetes mellitus, obesity, and coronary artery disease (CAD). Gut dysbiosis has also been associated with cardiac arrhythmias, including atrial fibrillation (AF) and ventricular arrhythmias (Figure).6-12

FDP04207264_F1

Whether gut dysbiosis is a cause or effect of the human disease process is unclear. While further research is warranted, some evidence of causation has been found. In 2018, Yoshida et al demonstrated an association between patients with CAD who had a significantly lower burden of the gut bacteria species Bacteroides vulgatus and Bacteroides dorei compared to that of patients without CAD. The study found that administration of these Bacteroides species reduced atherosclerotic lesion formation in atherosclerosis-prone mice.13 If altering gut microbial composition can affect the disease process, it may indicate a causative role for gut dysbiosis in disease pathogenesis. Furthermore, this finding also suggests agents may be used to alter the gut microbiome and potentially prevent and treat diseases. An altered gut microbiome may serve as an early marker for human disease, aiding in timely diagnosis and institution of disease-modifying treatments.

This review outlines the broad relationship of the pathways and intermediaries that may be involved in mediating the interaction between the gut microbiome and cardiac arrhythmias based on rapidly increasing evidence. A comprehensive search among PubMed and Google Scholar databases was conducted to find articles relevant to the topic.

Potential Intermediaries

Potential pathways for how the gut microbiome and cardiovascular system interact are subjects of active research. However, recent research may point to potential mechanisms of the association between the systems. The gut microbiome may influence human physiology through 3 principal routes: the autonomic nervous system, inflammatory pathways, and metabolic processes.

Autonomic Nervous System

The concept of bidirectional communication between the gut and central nervous system, known as the microbiota-gut-brain axis, is widely accepted.14 Proposed mediators of this interaction include the vagus nerve, the sympathetic nervous system, and the hypothalamic-pituitary-adrenal axis; cytokines produced by the immune system, tryptophan metabolism, and the production of short-chain fatty acids (SCFAs).15,16

The gut microbiome appears to have a direct impact on the autonomic nervous system, through which it can influence cardiovascular function. Muller et al described how the gut microbiome modulated gut-extrinsic sympathetic neurons and that the depletion of gut microbiota led to activation of both brainstem sensory nuclei and efferent sympathetic premotor glutamatergic neurons.16 Meng et al found that systemic injection of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) led to significantly increased activity in the paraventricular nucleus, a hypothalamic structure essential to the central autonomic network. Their study demonstrated that systemic TMAO also led to increased left stellate ganglion (LSG) activity, a known contributor to cardiac sympathetic tone.12

Inflammatory Pathways

Inflammatory responses are another pathway for the gut microbiome to influence the cardiovascular system. SCFAs are a set of gut microbial metabolites produced in the colon by bacterial fermentation and decomposition of resistant starches and dietary fibers.17 These metabolites are increasingly recognized for their role in modulating disease processes, including cardiac disease. Aguilar et al found that the progression of atherosclerosis was slowed in apolipoprotein E (Apo-E) knockout mice by a chow diet supplemented with butyrate, a SCFA, suggesting it is an atheroprotective therapeutic agent. Less adhesion and migration of macrophages, reduced inflammation, improved plaque stability, and lowered atherosclerosis progression.18 Wei et al demonstrated in animal models that direct microinjection of the proinflammatory factors interleukin (IL)-1Β and tumor necrosis factor (TNF)-αdirectly into the subfornical organ increased heart rate, mean blood pressure, and renal sympathetic nerve activity.19

Metabolic Processes

Serotonin (5-HT), a metabolite of tryptophan, is a neurotransmitter that regulates many bodily functions and plays a significant role in the microbiota-brain gut axis.20 Oral ingestion of the bacterial species Bifidobacterium infantis increased plasma tryptophan in rat models.21 Additionally, many other microorganisms, including species of Candida, Streptococcus, Escherichia, and Enterococcus are known to produce 5-HT.22 While a relationship between the gut microbiome and plasma 5-HT has been established, interactions between 5-HT and the cardiovascular system are complex. Research has shown that stimulation of 5-HT1A receptors produces bradycardic and vasopressor effects, while stimulation of the 5-HT2 receptor induces vasoconstriction and tachycardia.23

A high-fiber diet can lower the incidence of hypertension, although the mechanisms are not clear. One potential reason could be alteration in gut bacteria, as a diet high in fiber has been shown to increase the prevalence of acetate-producing bacteria.24

Atherosclerosis

Research investigating the relationship of the gut microbiome with arrhythmias is in its early stages; however, the connection of the gut microbiome and atherosclerosis is more established.25 Contemporary studies have shown various gut microorganisms associated with atherosclerosis.26 Jie et al reported that patients with atherosclerotic cardiovascular disease had increased Enterobacteriaceae loads and oral cavity-associated bacteria with lower levels of butyrate producing bacteria when compared with healthy controls.27 In addition, microbial metabolites such as TMAO appear to promote atherosclerosis by increasing vascular inflammation and platelet reactivity.26 Researchers are investigating the modulation of these associations to help reduce atherosclerotic burden. Kasahara et al found that Roseburia intestinalis could reduce atherosclerotic disease in mice through the production of butyrate.28 Roberts et al established that administration of TMAO inhibitors reduced TMAO levels while reducing thrombus formation without observable toxicity or increased bleeding risk.29

Atrial Arrhythmias

The gut microbiome can also specifically affect cardiac arrhythmogenesis, and multiple studies suggest possible mediators of this interaction. Certain gut microbiome derived metabolites like TMAO may have a role in promoting AF.30 Other gut microbial metabolites like lipopolysaccharides and indoxyl sulfate are implicated in atrial electrical instability.31,32 Microbe-derived free fatty acids such as palmitic acid and adrenic acid can precipitate arrhythmogenesis. 33,34 Preponderances of certain gut bacteria like Ruminococcus, Streptococcus, and Enterococcus, as well as reductions of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila have been detected in patients with AF.8 Tabata et al found that certain clusters of bacterial groups led by Ruminococcus species seem to show higher prevalence in patients with AF, whereas the genus Enterobacter was significantly lower compared with control subjects. That study also noted that gut microbial composition is affected by diet and antacid use.35 Gut microbiome-derived serotonin may be another mediator for AF, which may be related to the fact that 5-HT4 receptors are present in atrial tissue.36

Ventricular Arrhythmias

A critical component to the development of malignant ventricular arrhythmias is an imbalance in autonomic tone; in particular, the overactivation of the sympathetic nervous system.37 Animal models have shown that augmentation of the sympathetic nervous system plays an essential role in the subsequent development of ventricular arrhythmias. 38 Several studies have established the LSG as an important component of the cardiac sympathetic nervous system pathway. 38,39 Ablation of the LSG has been shown to effectively reduce the burden of malignant arrhythmias, further pointing toward the role of excess sympathetic activity.37,39 Stellate ganglion denervation has become an established method for managing life-threatening ventricular arrhythmias.40

Gut metabolites may have significant effects on cardiac sympathetic activity. Meng et al investigated the effect of TMAO on the LSG in animals and its overall effect on the incidence of ventricular arrhythmias under ischemic conditions. To fully explore this interaction, they examined the effect of TMAO on LSG function though 2 mechanisms: local administration of TMAO within the LSG and systemic administration of TMAO leading to activation of the central sympathetic nervous system. In both protocols, left anterior descending coronary artery occlusion was performed after TMAO administration. Injection of TMAO directly into the LSG was found to significantly increase the cardiac sympathetic tone and incidence of ventricular arrhythmias. In the systemic administration control arm, ventricular arrhythmias were also significantly increased.12

Increased inflammatory states appear to correlate with an increase in sympathetic tone and ventricular arrhythmias.12 In an animal study, direct injection of the proinflammatory factor IL-1Β into the LSG not only resulted in increased inflammation, but aggravated cardiac sympathetic remodeling. This led to a decreased effective refractory period and action potential duration, leading to an increased maximal slope of the restitution curve and higher occurrence of ventricular arrhythmias.41 Shi et al demonstrated that paraventricular nucleus microinjection with TNF-α and IL-1Β also enhanced the cardiac sympathetic afferent reflex, showing that these proinflammatory cytokines not only upregulate the inflammatory response, but can also have excitatory effects that stimulate sympathetic activity and have the potential to be proarrhythmic.19,42 Local and systemic administration of the gut microbe-derived TMAO increased the expression of IL-1Β and TNF-α, thus implicating the microbiome as a potential mediator of the inflammatory response and as another potential pathway for increased ventricular arrhythmias.12

The N-methyl-d-aspartate receptor (NMDAR) is found in multiple organs—including the heart—but more specifically in the conducting system and myocardium.43,44 Research has discovered an upregulation of NMDARs in the setting of cardiac sympathetic hyperinnervation in rat models both with healed myocardial necrotic injury and without. The infusion of their ligand, NMDA, provoked ventricular tachycardia and ventricular fibrillation in rat models with sympathetic hyperinnervation and healed myocardial necrotic injury.45 Another study found that NMDAR activation provoked ventricular arrhythmias, but also prolonged repolarization and induced electrical instability.46 Proinflammatory markers have been shown to upregulate the expression of NMDARs; more importantly, NMDAR expression has been shown to be significantly increased in the setting of TMAO administration.12,47,48

5-HT also appears to have a substantial association with ventricular arrhythmias in addition to atrial arrhythmias. el-Mahdy demonstrated in anesthetized rats with acute coronary ligation that systemic doses of 5-HT represented a significant dose-dependent increase in the duration of ventricular tachycardia and ventricular fibrillation, while also increasing the number of ventricular ectopic beats.49 Certain gut microorganisms are known to produce 5-HT, including those in the genera Streptococcus, Escherichia, and Enterococcus.22 Additionally, oral ingestion of the Bifidobacterium infantis increased plasma levels of tryptophan in rat models.21 The gut microbiome may have significant effects on plasma serotonin levels, and thus have the potential to alter the risk for ventricular arrhythmias.

The deleterious effects of the gut microbiome have been documented. However, it appears to have potential protective effects, and several studies point to the possible mechanisms of this beneficial interaction. Propionate is a SCFA microorganism produced by gut microbial fermentation.50 In a rat model study, Zhou et al found that infusion of sodium propionate significantly reduced ventricular arrhythmias during acute myocardial ischemia or burst stimulation, thus confirming cardioprotective effects.50,51

Proposed mechanisms for reduced susceptibility to ventricular arrhythmias with propionate infusion include parasympathetic activation via the gut-brain axis, anti-inflammatory pathways, and improved cardiac electrophysiology instability.50 In addition butyrate has been found to reduce inflammation and myocardial hypertrophy. Jiang et al demonstrated in rats postmyocardial infarction that butyrate promoted expression of anti-inflammatory M2 macrophage markers, decreased expressions of nerve growth factor and norepinephrine, and decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase. The cumulative impact of butyrate led to suppression of inflammation and the inhibition of sympathetic neural remodeling, ultimately resulting in improved cardiac function and reduction in ventricular arrhythmias after myocardial infarction.52

Gut bacteria-derived acetate-mediated reduction in cardiac fibrosis may be another mechanism for the effects on ventricular arrhythmias. Cardiac fibrosis and scar are established as the primary substrate for reentrant ventricular arrhythmias seen in various cardiomyopathies.

Future Directions

The microbiome residing in the human gut has a significant impact on cardiac arrhythmias, the details of which remain unknown. A likely bidirectional relationship exists in which the gut microbiome may affect arrhythmogenesis and in turn be affected by cardiac arrhythmias. The mechanisms of action are not well understood, but likely involve the autonomic nervous system, inflammation, and metabolic pathways.

The gut microbiome is a complex collection of heterogenous microorganisms that have dramatic effects on the human body. Additional research is necessary to identify further associations and causations of gut microorganisms with various human body processes, as well as cardiovascular disease. The microbiome has been shown to directly and indirectly influence the development of different disease states, including the cardiovascular system and cardiac arrhythmias. Several pathways have been proposed through which the gut microbiome can potentially affect cardiac arrhythmogenesis. There are likely several mechanisms simultaneously in operation. Understanding the role of human gut microbiome in the genesis of cardiac arrhythmias not only may improve our understanding of arrhythmias, but also may result in novel treatment options. This could potentially lead to the development of therapeutic options and strategies to modulate the gut microbiome to help detect, prevent, and treat cardiac arrhythmias.

References
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  28. Kasahara K, Krautkramer KA, Org E, et al. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat Microbiol. 2018;3(12):1461- 1471. doi:10.1038/s41564-018-0272-x
  29. Roberts AB, Gu X, Buffa JA, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med. 2018;24(9):1407-1417. doi:10.1038/s41591-018-0128-1
  30. Yu L, Meng G, Huang B, et al. A potential relationship between gut microbes and atrial fibrillation: trimethylamine N-oxide, a gut microbe-derived metabolite, facilitates the progression of atrial fibrillation. Int J Cardiol. 2018;255:92- 98. doi:10.1016/j.ijcard.2017.11.071
  31. Okazaki R, Iwasaki YK, Miyauchi Y, et al. Lipopolysaccharide induces atrial arrhythmogenesis via down-regulation of L-type Ca2+ channel genes in rats. Int Heart J. 2009;50(3):353-363. doi:10.1536/ihj.50.353
  32. Chen WT, Chen YC, Hsieh MH, et al. The uremic toxin indoxyl sulfate increases pulmonary vein and atrial arrhythmogenesis. J Cardiovasc Electrophysiol. 2015;26(2):203- 210. doi:10.1111/jce.12554
  33. Fretts AM, Mozaffarian D, Siscovick DS, et al. Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study. J Am Heart Assoc. 2014;3(3):e000889. doi:10.1161/JAHA.114.000889
  34. Horas HNS, Nishiumi S, Kawano Y, Kobayashi T, Yoshida M, Azuma T. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease. Arch Biochem Biophys. 2017;623-624:64-75. doi:10.1016/j.abb.2017.04.009
  35. Tabata T, Yamashita T, Hosomi K, et al. Gut microbial composition in patients with atrial fibrillation: effects of diet and drugs. Heart Vessels. 2021;36(1):105-114. doi:10.1007/s00380-020-01669-y
  36. López-Rodriguez ML, Benhamú B, Morcillo MJ, et al. 5-HT(4) receptor antagonists: structure-affinity relationships and ligand-receptor interactions. Curr Top Med Chem. 2002;2(6):625-641. doi:10.2174/1568026023393769
  37. Yu L, Zhou L, Cao G, et al. Optogenetic modulation of cardiac sympathetic nerve activity to prevent ventricular arrhythmias. J Am Coll Cardiol. 2017;70(22):2778-2790. doi:10.1016/j.jacc.2017.09.1107
  38. Schwartz PJ, Vanoli E. Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs. J Cardiovasc Pharmacol. 1981;3(6):1251-1259. doi:10.1097/00005344-198111000-00012
  39. Puddu PE, Jouve R, Langlet F, Guillen JC, Lanti M, Reale A. Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs. Circulation. 1988;77(4):935-946. doi:10.1161/01.cir.77.4.935
  40. Vaseghi M, Gima J, Kanaan C, et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and longterm follow-up. Heart Rhythm. 2014;11(3):360-366. doi:10.1016/j.hrthm.2013.11.028
  41. Wang M, Li S, Zhou X, et al. Increased inflammation promotes ventricular arrhythmia through aggravating left stellate ganglion remodeling in a canine ischemia model. Int J Cardiol. 2017;248:286-293. doi:10.1016/j.ijcard.2017.08.011
  42. Shi Z, Gan XB, Fan ZD, et al. Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats. Acta Physiol (Oxf). 2011;203(2):289-297. doi:10.1111/j.1748-1716.2011.02313.x
  43. Gill S, Veinot J, Kavanagh M, Pulido O. Human heart glutamate receptors - implications for toxicology, food safety, and drug discovery. Toxicol Pathol. 2007;35(3):411-417. doi:10.1080/01926230701230361
  44. Govoruskina N, Jakovljevic V, Zivkovic V, et al. The role of cardiac N-methyl-D-aspartate receptors in heart conditioning— effects on heart function and oxidative stress. Biomolecules. 2020;10(7):1065. doi:10.3390/biom10071065
  45. Lü J, Gao X, Gu J, et al. Nerve sprouting contributes to increased severity of ventricular tachyarrhythmias by upregulating iGluRs in rats with healed myocardial necrotic injury. J Mol Neurosci. 2012;48(2):448-455. doi:10.1007/s12031-012-9720-x
  46. Shi S, Liu T, Li Y, et al. Chronic N-methyl-D-aspartate receptor activation induces cardiac electrical remodeling and increases susceptibility to ventricular arrhythmias. Pacing Clin Electrophysiol. 2014;37(10):1367-1377. doi:10.1111/pace.12430
  47. Zhang Z, Bassam B, Thomas AG, et al. Maternal inflammation leads to impaired glutamate homeostasis and upregulation of glutamate carboxypeptidase II in activated microglia in the fetal/newborn rabbit brain. Neurobiol Dis. 2016;94:116-128. doi:10.1016/j.nbd.2016.06.010
  48. Wu LJ, Toyoda H, Zhao MG, et al. Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci. 2005;25(48):11107-11116. doi:10.1523/JNEUROSCI.1678-05.2005
  49. el-Mahdy SA. 5-hydroxytryptamine (serotonin) enhances ventricular arrhythmias induced by acute coronary artery ligation in rats. Res Commun Chem Pathol Pharmacol. 1990;68(3):383-386.
  50. Zhou M, Li D, Xie K, et al. The short-chain fatty acid propionate improved ventricular electrical remodeling in a rat model with myocardial infarction. Food Funct. 2021;12(24):12580-12593. doi:10.1039/d1fo02040d
  51. Bartolomaeus H, Balogh A, Yakoub M, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation. 2019;139(11):1407-1421. doi:10.1161/CIRCULATIONAHA.118.036652
  52. Jiang X, Huang X, Tong Y, Gao H. Butyrate improves cardiac function and sympathetic neural remodeling following myocardial infarction in rats. Can J Physiol Pharmacol. 2020;98(6):391-399. doi:10.1139/cjpp-2019-0531
References
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  2. Karlsson F, Tremaroli V, Nielsen J, Bäckhed F. Assessing the human gut microbiota in metabolic diseases. Diabetes. 2013;62(10):3341-3349. doi:10.2337/db13-0844
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  5. Integrative HMP (iHMP) Research Network Consortium. The integrative human microbiome project. Nature. 2019;569(7758):641-648. doi:10.1038/s41586-019-1238-8
  6. Zubcevic J, Richards EM, Yang T, et al. Impaired autonomic nervous system-microbiome circuit in hypertension. Circ Res. 2019;125(1):104-116. doi:10.1161/CIRCRESAHA.119.313965
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  8. Zuo K, Li J, Li K, et al. Disordered gut microbiota and alterations in metabolic patterns are associated with atrial fibrillation. Gigascience. 2019;8(6):giz058. doi:10.1093/gigascience/giz058
  9. Li J, Zhao F, Wang Y, et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5(1):14. doi:10.1186/s40168-016-0222-x
  10. Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55-60. doi:10.1038/nature11450
  11. Chang CJ, Lin CS, Lu CC, et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun. 2015;6:7489. doi:10.1038/ncomms8489
  12. Meng G, Zhou X, Wang M, et al. Gut microbederived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways. EBioMedicine. 2019;44:656-664. doi:10.1016/j.ebiom.2019.03.066
  13. Yoshida N, Emoto T, Yamashita T, et al. Bacteroides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis. Circulation. 2018;138(22):2486-2498. doi:10.1161/CIRCULATIONAHA.118.033714
  14. Cussotto S, Sandhu KV, Dinan TG, Cryan JF. The neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective. Front Neuroendocrinol. 2018;51:80-101. doi:10.1016/j.yfrne.2018.04.002
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  16. Muller PA, Schneeberger M, Matheis F, et al. Microbiota modulate sympathetic neurons via a gutbrain circuit. Nature. 2020;583(7816):441-446. doi:10.1038/s41586-020-2474-7
  17. Ohira H, Tsutsui W, Fujioka Y. Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? J Atheroscler Thromb. 2017;24(7):660-672. doi:10.5551/jat.RV17006
  18. Aguilar EC, Leonel AJ, Teixeira LG, et al. Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFêB activation. Nutr Metab Cardiovasc Dis. 2014;24(6):606-613. doi:10.1016/j.numecd.2014.01.002
  19. Wei SG, Yu Y, Zhang ZH, Felder RB. Proinflammatory cytokines upregulate sympathoexcit - atory mechanisms in the subfornical organ of the rat. Hypertension. 2015;65(5):1126-1133. doi:10.1161/HYPERTENSIONAHA.114.05112
  20. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013;74(10):720- 726. doi:10.1016/j.biopsych.2013.05.001
  21. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43(2):164-174. doi:10.1016/j.jpsychires.2008.03.009
  22. Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays. 2011;33(8):574-581. doi:10.1002/bies.201100024
  23. Yusuf S, Al-Saady N, Camm AJ. 5-hydroxytryptamine and atrial fibrillation: how significant is this piece in the puzzle? J Cardiovasc Electrophysiol. 2003;14(2):209-214. doi:10.1046/j.1540-8167.2003.02381.x
  24. Marques FZ, Nelson E, Chu PY, et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation. 2017;135(10):964-977. doi:10.1161/CIRCULATIONAHA.116.024545
  25. Björkegren JLM, Lusis AJ. Atherosclerosis: recent developments. Cell. 2022;185(10):1630-1645. doi:10.1016/j.cell.2022.04.004
  26. Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(16):2089-2105. doi:10.1016/j.jacc.2019.03.024
  27. Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8(1):845. doi:10.1038/s41467-017-00900-1
  28. Kasahara K, Krautkramer KA, Org E, et al. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat Microbiol. 2018;3(12):1461- 1471. doi:10.1038/s41564-018-0272-x
  29. Roberts AB, Gu X, Buffa JA, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med. 2018;24(9):1407-1417. doi:10.1038/s41591-018-0128-1
  30. Yu L, Meng G, Huang B, et al. A potential relationship between gut microbes and atrial fibrillation: trimethylamine N-oxide, a gut microbe-derived metabolite, facilitates the progression of atrial fibrillation. Int J Cardiol. 2018;255:92- 98. doi:10.1016/j.ijcard.2017.11.071
  31. Okazaki R, Iwasaki YK, Miyauchi Y, et al. Lipopolysaccharide induces atrial arrhythmogenesis via down-regulation of L-type Ca2+ channel genes in rats. Int Heart J. 2009;50(3):353-363. doi:10.1536/ihj.50.353
  32. Chen WT, Chen YC, Hsieh MH, et al. The uremic toxin indoxyl sulfate increases pulmonary vein and atrial arrhythmogenesis. J Cardiovasc Electrophysiol. 2015;26(2):203- 210. doi:10.1111/jce.12554
  33. Fretts AM, Mozaffarian D, Siscovick DS, et al. Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study. J Am Heart Assoc. 2014;3(3):e000889. doi:10.1161/JAHA.114.000889
  34. Horas HNS, Nishiumi S, Kawano Y, Kobayashi T, Yoshida M, Azuma T. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease. Arch Biochem Biophys. 2017;623-624:64-75. doi:10.1016/j.abb.2017.04.009
  35. Tabata T, Yamashita T, Hosomi K, et al. Gut microbial composition in patients with atrial fibrillation: effects of diet and drugs. Heart Vessels. 2021;36(1):105-114. doi:10.1007/s00380-020-01669-y
  36. López-Rodriguez ML, Benhamú B, Morcillo MJ, et al. 5-HT(4) receptor antagonists: structure-affinity relationships and ligand-receptor interactions. Curr Top Med Chem. 2002;2(6):625-641. doi:10.2174/1568026023393769
  37. Yu L, Zhou L, Cao G, et al. Optogenetic modulation of cardiac sympathetic nerve activity to prevent ventricular arrhythmias. J Am Coll Cardiol. 2017;70(22):2778-2790. doi:10.1016/j.jacc.2017.09.1107
  38. Schwartz PJ, Vanoli E. Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs. J Cardiovasc Pharmacol. 1981;3(6):1251-1259. doi:10.1097/00005344-198111000-00012
  39. Puddu PE, Jouve R, Langlet F, Guillen JC, Lanti M, Reale A. Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs. Circulation. 1988;77(4):935-946. doi:10.1161/01.cir.77.4.935
  40. Vaseghi M, Gima J, Kanaan C, et al. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and longterm follow-up. Heart Rhythm. 2014;11(3):360-366. doi:10.1016/j.hrthm.2013.11.028
  41. Wang M, Li S, Zhou X, et al. Increased inflammation promotes ventricular arrhythmia through aggravating left stellate ganglion remodeling in a canine ischemia model. Int J Cardiol. 2017;248:286-293. doi:10.1016/j.ijcard.2017.08.011
  42. Shi Z, Gan XB, Fan ZD, et al. Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats. Acta Physiol (Oxf). 2011;203(2):289-297. doi:10.1111/j.1748-1716.2011.02313.x
  43. Gill S, Veinot J, Kavanagh M, Pulido O. Human heart glutamate receptors - implications for toxicology, food safety, and drug discovery. Toxicol Pathol. 2007;35(3):411-417. doi:10.1080/01926230701230361
  44. Govoruskina N, Jakovljevic V, Zivkovic V, et al. The role of cardiac N-methyl-D-aspartate receptors in heart conditioning— effects on heart function and oxidative stress. Biomolecules. 2020;10(7):1065. doi:10.3390/biom10071065
  45. Lü J, Gao X, Gu J, et al. Nerve sprouting contributes to increased severity of ventricular tachyarrhythmias by upregulating iGluRs in rats with healed myocardial necrotic injury. J Mol Neurosci. 2012;48(2):448-455. doi:10.1007/s12031-012-9720-x
  46. Shi S, Liu T, Li Y, et al. Chronic N-methyl-D-aspartate receptor activation induces cardiac electrical remodeling and increases susceptibility to ventricular arrhythmias. Pacing Clin Electrophysiol. 2014;37(10):1367-1377. doi:10.1111/pace.12430
  47. Zhang Z, Bassam B, Thomas AG, et al. Maternal inflammation leads to impaired glutamate homeostasis and upregulation of glutamate carboxypeptidase II in activated microglia in the fetal/newborn rabbit brain. Neurobiol Dis. 2016;94:116-128. doi:10.1016/j.nbd.2016.06.010
  48. Wu LJ, Toyoda H, Zhao MG, et al. Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci. 2005;25(48):11107-11116. doi:10.1523/JNEUROSCI.1678-05.2005
  49. el-Mahdy SA. 5-hydroxytryptamine (serotonin) enhances ventricular arrhythmias induced by acute coronary artery ligation in rats. Res Commun Chem Pathol Pharmacol. 1990;68(3):383-386.
  50. Zhou M, Li D, Xie K, et al. The short-chain fatty acid propionate improved ventricular electrical remodeling in a rat model with myocardial infarction. Food Funct. 2021;12(24):12580-12593. doi:10.1039/d1fo02040d
  51. Bartolomaeus H, Balogh A, Yakoub M, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation. 2019;139(11):1407-1421. doi:10.1161/CIRCULATIONAHA.118.036652
  52. Jiang X, Huang X, Tong Y, Gao H. Butyrate improves cardiac function and sympathetic neural remodeling following myocardial infarction in rats. Can J Physiol Pharmacol. 2020;98(6):391-399. doi:10.1139/cjpp-2019-0531
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References
  1. Jones JM. LGBTQ+ identification in U.S. rises to 9.3%. Gallup.com website. February 20, 2025. Accessed March 4, 2025. https://news.gallup.com/poll/656708/lgbtq-identification-rises.aspx.
  2. Newman KL, Vélez C, Paul S, Radix AE, Streed CG Jr, Targownik LE. Research Considerations in Digestive and Liver Disease in Transgender and Gender-Diverse Populations. Gastroenterology. 2023;165(3):523-528.e1. doi:10.1053/j.gastro.2023.07.011
  3. Vélez C, Newman KL, Paul S, Berli JU, Tangpricha V, Targownik LE. Approaching Digestive Health Care in Transgender and Gender-Diverse Communities. Clin Gastroenterol Hepatol. 2024;22(3):441-447.e2. doi:10.1016/j.cgh.2023.12.001
  4. Condray CD, Newman KL, Chedid VG. Consequences of bathroom restriction on transgender individuals with gastrointestinal conditions in the United States. Nat Rev Gastroenterol Hepatol. 2024;21(10):662-663. doi:10.1038/s41575-024-00975-4
  5. Tsai C, Abdelhalim S, Wong S-Y, Xie X, Agrawal M, Keefer LA. Trauma-Informed Care in Gastroenterology: A Survey of Provider Attitudes, Knowledge, and Skills. Clin Gastroenterol Hepatol. 2024 Oct 24:S1542-3565(24)00953-4. doi:10.1016/j.cgh.2024.09.015
  6. Newman KL, Chedid VG, Boden EK. A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals. Gastroenterology. 2023;164(6):866-871. doi:10.1053/j.gastro.2022.11.048
  7. Hassan B, Suchan A, Brown M, Kishan A, Liang F, Truta B. The Impact of Hormone Therapy on Inflammatory Bowel Disease in Transgender and Nonbinary Individuals. Inflamm Bowel Dis. 2024 Oct 16:izae236. doi:10.1093/ibd/izae236
  8. Elhence H, Dodge JL, Kahn JA, Lee BP. Characteristics and Outcomes Among US Commercially Insured Transgender Adults With Cirrhosis: A National Cohort Study. Am J Gastroenterol. 2024;119(12):2455-2461. doi:10.14309/ajg.0000000000002907
  9. Stier EA, Clarke MA, Deshmukh AA, et al. International Anal Neoplasia Society’s consensus guidelines for anal cancer screening. Int J Cancer. 2024;154(10):1694-1702. doi:10.1002/ijc.34850
  10. Nash R, Ward KC, Jemal A, Sandberg DE, Tangpricha V, Goodman M. Frequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data. Cancer Epidemiol. 2018;54:1-6. doi:10.1016/j.canep.2018.02.008
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Kira Newman, MD, PhD
Clinical Assistant Professor, Department of
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Hepatology, University of Michigan,
Ann Arbor, Michigan

Disclosures: Received research grant from: Pfizer

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Kira Newman, MD, PhD
Clinical Assistant Professor, Department of
Medicine, Division of Gastroenterology and
Hepatology, University of Michigan,
Ann Arbor, Michigan

Disclosures: Received research grant from: Pfizer

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Kira Newman, MD, PhD
Clinical Assistant Professor, Department of
Medicine, Division of Gastroenterology and
Hepatology, University of Michigan,
Ann Arbor, Michigan

Disclosures: Received research grant from: Pfizer

Click to view more from Gastroenterology Data Trends. 

Click to view more from Gastroenterology Data Trends. 

References
  1. Jones JM. LGBTQ+ identification in U.S. rises to 9.3%. Gallup.com website. February 20, 2025. Accessed March 4, 2025. https://news.gallup.com/poll/656708/lgbtq-identification-rises.aspx.
  2. Newman KL, Vélez C, Paul S, Radix AE, Streed CG Jr, Targownik LE. Research Considerations in Digestive and Liver Disease in Transgender and Gender-Diverse Populations. Gastroenterology. 2023;165(3):523-528.e1. doi:10.1053/j.gastro.2023.07.011
  3. Vélez C, Newman KL, Paul S, Berli JU, Tangpricha V, Targownik LE. Approaching Digestive Health Care in Transgender and Gender-Diverse Communities. Clin Gastroenterol Hepatol. 2024;22(3):441-447.e2. doi:10.1016/j.cgh.2023.12.001
  4. Condray CD, Newman KL, Chedid VG. Consequences of bathroom restriction on transgender individuals with gastrointestinal conditions in the United States. Nat Rev Gastroenterol Hepatol. 2024;21(10):662-663. doi:10.1038/s41575-024-00975-4
  5. Tsai C, Abdelhalim S, Wong S-Y, Xie X, Agrawal M, Keefer LA. Trauma-Informed Care in Gastroenterology: A Survey of Provider Attitudes, Knowledge, and Skills. Clin Gastroenterol Hepatol. 2024 Oct 24:S1542-3565(24)00953-4. doi:10.1016/j.cgh.2024.09.015
  6. Newman KL, Chedid VG, Boden EK. A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals. Gastroenterology. 2023;164(6):866-871. doi:10.1053/j.gastro.2022.11.048
  7. Hassan B, Suchan A, Brown M, Kishan A, Liang F, Truta B. The Impact of Hormone Therapy on Inflammatory Bowel Disease in Transgender and Nonbinary Individuals. Inflamm Bowel Dis. 2024 Oct 16:izae236. doi:10.1093/ibd/izae236
  8. Elhence H, Dodge JL, Kahn JA, Lee BP. Characteristics and Outcomes Among US Commercially Insured Transgender Adults With Cirrhosis: A National Cohort Study. Am J Gastroenterol. 2024;119(12):2455-2461. doi:10.14309/ajg.0000000000002907
  9. Stier EA, Clarke MA, Deshmukh AA, et al. International Anal Neoplasia Society’s consensus guidelines for anal cancer screening. Int J Cancer. 2024;154(10):1694-1702. doi:10.1002/ijc.34850
  10. Nash R, Ward KC, Jemal A, Sandberg DE, Tangpricha V, Goodman M. Frequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data. Cancer Epidemiol. 2018;54:1-6. doi:10.1016/j.canep.2018.02.008
References
  1. Jones JM. LGBTQ+ identification in U.S. rises to 9.3%. Gallup.com website. February 20, 2025. Accessed March 4, 2025. https://news.gallup.com/poll/656708/lgbtq-identification-rises.aspx.
  2. Newman KL, Vélez C, Paul S, Radix AE, Streed CG Jr, Targownik LE. Research Considerations in Digestive and Liver Disease in Transgender and Gender-Diverse Populations. Gastroenterology. 2023;165(3):523-528.e1. doi:10.1053/j.gastro.2023.07.011
  3. Vélez C, Newman KL, Paul S, Berli JU, Tangpricha V, Targownik LE. Approaching Digestive Health Care in Transgender and Gender-Diverse Communities. Clin Gastroenterol Hepatol. 2024;22(3):441-447.e2. doi:10.1016/j.cgh.2023.12.001
  4. Condray CD, Newman KL, Chedid VG. Consequences of bathroom restriction on transgender individuals with gastrointestinal conditions in the United States. Nat Rev Gastroenterol Hepatol. 2024;21(10):662-663. doi:10.1038/s41575-024-00975-4
  5. Tsai C, Abdelhalim S, Wong S-Y, Xie X, Agrawal M, Keefer LA. Trauma-Informed Care in Gastroenterology: A Survey of Provider Attitudes, Knowledge, and Skills. Clin Gastroenterol Hepatol. 2024 Oct 24:S1542-3565(24)00953-4. doi:10.1016/j.cgh.2024.09.015
  6. Newman KL, Chedid VG, Boden EK. A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals. Gastroenterology. 2023;164(6):866-871. doi:10.1053/j.gastro.2022.11.048
  7. Hassan B, Suchan A, Brown M, Kishan A, Liang F, Truta B. The Impact of Hormone Therapy on Inflammatory Bowel Disease in Transgender and Nonbinary Individuals. Inflamm Bowel Dis. 2024 Oct 16:izae236. doi:10.1093/ibd/izae236
  8. Elhence H, Dodge JL, Kahn JA, Lee BP. Characteristics and Outcomes Among US Commercially Insured Transgender Adults With Cirrhosis: A National Cohort Study. Am J Gastroenterol. 2024;119(12):2455-2461. doi:10.14309/ajg.0000000000002907
  9. Stier EA, Clarke MA, Deshmukh AA, et al. International Anal Neoplasia Society’s consensus guidelines for anal cancer screening. Int J Cancer. 2024;154(10):1694-1702. doi:10.1002/ijc.34850
  10. Nash R, Ward KC, Jemal A, Sandberg DE, Tangpricha V, Goodman M. Frequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data. Cancer Epidemiol. 2018;54:1-6. doi:10.1016/j.canep.2018.02.008
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Overall, 1.3% of US adults identify as transgender or gender-diverse (TGD), with a higher prevalence of TGD-identified people in younger generations.1,2 This finding suggests that all clinicians will provide care to TGD patients.1,2 TGD individuals are more likely to experience health care discrimination than cisgender individuals, resulting in reduced access to and utilization of care.2,3 It is important for health care providers, including gastroenterologists and hepatologists, to create a welcoming and gender-affirming environment—offering single-occupancy handicap-accessible bathrooms, displaying nondiscrimination policies, using inclusive intake forms, and providing training for clinicians to increase knowledge of TGD health needs and address biases.3,4 This type of environment can help reduce negative outcomes for TGD patients seeking care.3,4 Understanding the minority stress model and trauma-informed care approaches can also be useful for caring for TGD patients.2,5 A recent study found that up to 51% of gastrointestinal (GI) providers are not at all familiar with trauma-informed care, highlighting the need for further education.5

High-quality research on GI conditions in TGD populations is limited, and potential proposed biological effects of gender-affirming hormone therapy (GAHT) are still theoretical. Studies have shown that the prevalence of inflammatory bowel disease (IBD) is similar between TGD and cisgender individuals, and that GAHT does not affect flare-ups of IBD, although the sample sizes have been small.6,7 Hepatic conditions such as cirrhosis were shown to be more common in TGD communities, which may be largely due to preventable causes of cirrhosis (e.g., alcohol-associated or viral etiologies) and delayed diagnosis and treatment before progression.8 More research is needed in TGD patients with GI conditions, and best practices for their design and conduct, such as partnering with TGD people, designing studies with cultural humility in mind, using rigorous research methods, and checking for implicit biases in studies, must be followed.2

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Alagille Syndrome: Epidemiology and Management of a Rare Genetic Disease

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Alagille Syndrome: Epidemiology and Management of a Rare Genetic Disease

References
  1. Yan J, Huang Y, Cao L, et al. Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome. BMC Pediatr. 2024;24(1):532. doi:10.1186/s12887-024-04973-y 

  2. Cheng K, Rosenthal P. Diagnosis and management of Alagille and progressive familial intrahepatic cholestasis. Hepatol Commun. 2023 Dec 7;7(12):e0314. doi:10.1097/HC9.0000000000000314

  3. Global Allagile Alliance, GALA, website. The GALA Study. Published 2022. Accessed January 27, 2025.  https://www.galastudy.com/ 

  4. Karim F, Hiremath G, Samayoa JC, Said SM. Complex Pulmonary Artery Rehabilitation in Children with Alagille Syndrome: An Early Single-Center Experience of a Successful Collaborative Work. J Cardiovasc Dev Dis. 2024;11(8):232. doi:10.3390/jcdd11080232

  5. Vandriel SM, Loomes K, Sokal E, et al. Surgical biliary diversion is associated with an increased risk of liver transplantation or death in Alagille syndrome. AASLD Liver Meeting (Boston, USA. 09/11/2023 to 13/11/2023). In: Hepatology. 2023;78(S1):S1-S2154. Abstract 12 (2023). http://hdl.handle.net/2078.1/279387

  6. Hansen BE, Vandriel SM, Vig P, et al; the Global ALagille Alliance (GALA) Study Group. Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA. Hepatology. 2024;79(6):1279-1292. doi:10.1097/HEP.0000000000000727

  7. Vandriel SM, Li L-T, She H, et al; the Global ALagille Alliance (GALA) Study Group. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. Hepatology. 2023;77(2):512-529. doi:10.1002/hep.32761

  8. Murillo Perez CF, Vandriel SM, Sokal E, et al. Serum bile acids are associated with native liver survival in patients with Alagille syndrome: Results from the GALA Study Group. AASLD Liver Meeting (Boston, USA, 09/11/2023 to 13/11/2023). In: Hepatology. 2023;78(S1):S1-S2154. Abstract 121 (2023). http://hdl.handle.net/2078.1/279390

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Alisha Mavis, MD
Clinical Assistant Professor, Department of Pediatrics
Wake Forest University School of Medicine; 
Physician, Department of Pediatric Gastroenterology, Hepatology, and Nutrition
Medical Center
Charlotte, North Carolina 

Alisha Mavis, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Ipsen; Mirum; Alexion Serve(d) as a member of a speakers bureau for: Ipsen; Mirum; Alexion

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Alisha Mavis, MD
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Wake Forest University School of Medicine; 
Physician, Department of Pediatric Gastroenterology, Hepatology, and Nutrition
Medical Center
Charlotte, North Carolina 

Alisha Mavis, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Ipsen; Mirum; Alexion Serve(d) as a member of a speakers bureau for: Ipsen; Mirum; Alexion

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Alisha Mavis, MD
Clinical Assistant Professor, Department of Pediatrics
Wake Forest University School of Medicine; 
Physician, Department of Pediatric Gastroenterology, Hepatology, and Nutrition
Medical Center
Charlotte, North Carolina 

Alisha Mavis, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Ipsen; Mirum; Alexion Serve(d) as a member of a speakers bureau for: Ipsen; Mirum; Alexion

References
  1. Yan J, Huang Y, Cao L, et al. Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome. BMC Pediatr. 2024;24(1):532. doi:10.1186/s12887-024-04973-y 

  2. Cheng K, Rosenthal P. Diagnosis and management of Alagille and progressive familial intrahepatic cholestasis. Hepatol Commun. 2023 Dec 7;7(12):e0314. doi:10.1097/HC9.0000000000000314

  3. Global Allagile Alliance, GALA, website. The GALA Study. Published 2022. Accessed January 27, 2025.  https://www.galastudy.com/ 

  4. Karim F, Hiremath G, Samayoa JC, Said SM. Complex Pulmonary Artery Rehabilitation in Children with Alagille Syndrome: An Early Single-Center Experience of a Successful Collaborative Work. J Cardiovasc Dev Dis. 2024;11(8):232. doi:10.3390/jcdd11080232

  5. Vandriel SM, Loomes K, Sokal E, et al. Surgical biliary diversion is associated with an increased risk of liver transplantation or death in Alagille syndrome. AASLD Liver Meeting (Boston, USA. 09/11/2023 to 13/11/2023). In: Hepatology. 2023;78(S1):S1-S2154. Abstract 12 (2023). http://hdl.handle.net/2078.1/279387

  6. Hansen BE, Vandriel SM, Vig P, et al; the Global ALagille Alliance (GALA) Study Group. Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA. Hepatology. 2024;79(6):1279-1292. doi:10.1097/HEP.0000000000000727

  7. Vandriel SM, Li L-T, She H, et al; the Global ALagille Alliance (GALA) Study Group. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. Hepatology. 2023;77(2):512-529. doi:10.1002/hep.32761

  8. Murillo Perez CF, Vandriel SM, Sokal E, et al. Serum bile acids are associated with native liver survival in patients with Alagille syndrome: Results from the GALA Study Group. AASLD Liver Meeting (Boston, USA, 09/11/2023 to 13/11/2023). In: Hepatology. 2023;78(S1):S1-S2154. Abstract 121 (2023). http://hdl.handle.net/2078.1/279390

References
  1. Yan J, Huang Y, Cao L, et al. Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome. BMC Pediatr. 2024;24(1):532. doi:10.1186/s12887-024-04973-y 

  2. Cheng K, Rosenthal P. Diagnosis and management of Alagille and progressive familial intrahepatic cholestasis. Hepatol Commun. 2023 Dec 7;7(12):e0314. doi:10.1097/HC9.0000000000000314

  3. Global Allagile Alliance, GALA, website. The GALA Study. Published 2022. Accessed January 27, 2025.  https://www.galastudy.com/ 

  4. Karim F, Hiremath G, Samayoa JC, Said SM. Complex Pulmonary Artery Rehabilitation in Children with Alagille Syndrome: An Early Single-Center Experience of a Successful Collaborative Work. J Cardiovasc Dev Dis. 2024;11(8):232. doi:10.3390/jcdd11080232

  5. Vandriel SM, Loomes K, Sokal E, et al. Surgical biliary diversion is associated with an increased risk of liver transplantation or death in Alagille syndrome. AASLD Liver Meeting (Boston, USA. 09/11/2023 to 13/11/2023). In: Hepatology. 2023;78(S1):S1-S2154. Abstract 12 (2023). http://hdl.handle.net/2078.1/279387

  6. Hansen BE, Vandriel SM, Vig P, et al; the Global ALagille Alliance (GALA) Study Group. Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA. Hepatology. 2024;79(6):1279-1292. doi:10.1097/HEP.0000000000000727

  7. Vandriel SM, Li L-T, She H, et al; the Global ALagille Alliance (GALA) Study Group. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. Hepatology. 2023;77(2):512-529. doi:10.1002/hep.32761

  8. Murillo Perez CF, Vandriel SM, Sokal E, et al. Serum bile acids are associated with native liver survival in patients with Alagille syndrome: Results from the GALA Study Group. AASLD Liver Meeting (Boston, USA, 09/11/2023 to 13/11/2023). In: Hepatology. 2023;78(S1):S1-S2154. Abstract 121 (2023). http://hdl.handle.net/2078.1/279390

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Alagille Syndrome: Epidemiology and Management of a Rare Genetic Disease

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Alagille syndrome (ALGS) is a rare, genetically inherited multisystem disorder that typically presents in early childhood.1 The condition is attributed to pathogenic variants in the Notch Homolog 2 (NOTCH2) and jagged canonical Notch ligand 1 (JAG1) genes.1,2 The incidence of ALGS is estimated to be between 1 in 30,000 to 1 in 1,000,000 individuals.1

This condition is characterized by a range of symptoms and anomalies, most notably cholestasis, which can lead to severe liver disease.1 These anomalies can include renal anomalies, cardiac abnormalities, vascular malformations, bone deformities, eye irregularities, and developmental delays.1,3 Genetic testing and diagnostic imaging are key in diagnosis.1 Treatment includes medication to address symptoms─especially pruritus─and liver transplant is not uncommon in these patients.2

The Global Alagille Alliance (GALA) Study comprises more than 100 physicians, surgeons, scientists, and research coordinators from 32 countries around the world. This study aims to produce several significant findings regarding ALGS that contribute to a better understanding of the condition and help improve clinical decision-making and patient care.3,4

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Gastroenterology Data Trends 2025

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Gastroenterology Data Trends 2025

GI & Hepatology News and the American Gastroenterological Association (AGA) present Gastroenterology Data Trends 2025, a special report on hot topics in GI told through original infographics and visual storytelling.

 

In this issue: 

 

The Role of Bedside Intestinal Ultrasound in IBD Management
Bincy Abraham, MD, MS

Obesity Management in the Era of GLP-1: The Role of GLP-1 RAs
Michael Camilleri, MD, MPhil, DSc

Ergonomics in Endoscopy
Amandeep K. Shergill, MD, MS

Optimizing the Delivery of GI Care in Transgender and Gender-Diverse Communities
Kira Newman, MD, PhD

New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis
Evan S. Dellon, MD, MPH

New and Emerging Treatments for MASLD/MASH
Naim Alkhouri, MD

Advances in Screening for Barrett’s Esophagus and Esophageal Adenocarcinoma
Joel Rubenstein, MD, MS

Alagille Syndrome: Epidemiology and Management of a Rare Genetic Disease
Alisha Mavis, MD

IBS: Mental Health Factors and Comorbidities
Lin Chang, MD, and Laurie A. Keefer, PhD

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GI & Hepatology News and the American Gastroenterological Association (AGA) present Gastroenterology Data Trends 2025, a special report on hot topics in GI told through original infographics and visual storytelling.

 

In this issue: 

 

The Role of Bedside Intestinal Ultrasound in IBD Management
Bincy Abraham, MD, MS

Obesity Management in the Era of GLP-1: The Role of GLP-1 RAs
Michael Camilleri, MD, MPhil, DSc

Ergonomics in Endoscopy
Amandeep K. Shergill, MD, MS

Optimizing the Delivery of GI Care in Transgender and Gender-Diverse Communities
Kira Newman, MD, PhD

New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis
Evan S. Dellon, MD, MPH

New and Emerging Treatments for MASLD/MASH
Naim Alkhouri, MD

Advances in Screening for Barrett’s Esophagus and Esophageal Adenocarcinoma
Joel Rubenstein, MD, MS

Alagille Syndrome: Epidemiology and Management of a Rare Genetic Disease
Alisha Mavis, MD

IBS: Mental Health Factors and Comorbidities
Lin Chang, MD, and Laurie A. Keefer, PhD

GI & Hepatology News and the American Gastroenterological Association (AGA) present Gastroenterology Data Trends 2025, a special report on hot topics in GI told through original infographics and visual storytelling.

 

In this issue: 

 

The Role of Bedside Intestinal Ultrasound in IBD Management
Bincy Abraham, MD, MS

Obesity Management in the Era of GLP-1: The Role of GLP-1 RAs
Michael Camilleri, MD, MPhil, DSc

Ergonomics in Endoscopy
Amandeep K. Shergill, MD, MS

Optimizing the Delivery of GI Care in Transgender and Gender-Diverse Communities
Kira Newman, MD, PhD

New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis
Evan S. Dellon, MD, MPH

New and Emerging Treatments for MASLD/MASH
Naim Alkhouri, MD

Advances in Screening for Barrett’s Esophagus and Esophageal Adenocarcinoma
Joel Rubenstein, MD, MS

Alagille Syndrome: Epidemiology and Management of a Rare Genetic Disease
Alisha Mavis, MD

IBS: Mental Health Factors and Comorbidities
Lin Chang, MD, and Laurie A. Keefer, PhD

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Gastroenterology Data Trends 2025

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New Model Estimates Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B

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A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

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A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

A new prognostic model could potentially predict and stratify the risk for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) who are noncirrhotic and not indicated for antiviral treatment.

The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.

“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.

“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”

The study was published in Annals of Internal Medicine.

 

Validating reREACH-B

During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.

In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.

In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).

The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.

Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.

In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.

In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.

Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.

Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.

For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.

In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.

“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.

 

Considering Prognostic Models

This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.

“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”

For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.

“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”

The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

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Around 5% of US Population Diagnosed With Autoimmune Disease

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TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

  • Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
  • They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
  • An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
  • A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

  • More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
  • Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
  • Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
  • Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

  • Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
  • They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
  • An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
  • A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

  • More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
  • Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
  • Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
  • Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

  • Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
  • They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
  • An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
  • A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

  • More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
  • Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
  • Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
  • Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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Highly Contagious Norovirus Cases Spike This Season

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Norovirus cases continue to rise in the United States this winter, at levels higher than the same time period in previous years, according to the latest data from the Centers for Disease Control and Prevention (CDC).

Current data from the CDC’s NoroSTAT monitoring system show 495 reported outbreaks during the period from August 1, 2024, to December 11, 2024, compared with 363 outbreaks during the same period last year. In addition, the total number of norovirus outbreaks in the current season are higher than those reported in the seasonal years: 2012-2020 and 2021-2024.

Circulating strains of norovirus change over time, which can affect disease burden and potential disease severity, Sara Mirza, MD, an epidemiologist in the CDC’s Division of Viral Diseases, said in an interview.

The numbers for the 2024 norovirus season (considered approximately November to April) have reached or exceeded the case numbers seen before the COVID-19 pandemic, Mirza said.

The increase in cases may be caused in part by a new predominant strain of norovirus. “For the fall/winter of 2024-2025 season, genogroup 2, genotype 17, known as GII.17, has become the most detected genotype (strain) in the US among laboratory confirmed outbreaks reported to CDC,” said Mirza. “At this time, there is no indication that GII.17 causes more severe illness or affects one population more than another, but we are continuing to conduct surveillance to assess,” she added.

 

Clinical Takeaways

“Norovirus affects all ages, but young children and older adults are most at risk from more severe outcomes,” said Mirza.

“Clinicians treating older patients for acute gastroenteritis should be aware of these elevated risks and be sure to include norovirus as a potentially serious diagnosis, particularly in vulnerable patients with other diseases and those living in congregate settings, such as nursing homes,” she said.

When treating a patient with norovirus during an outbreak, use soap and water for hand hygiene after caring for patients with suspected or confirmed norovirus gastroenteritis, said Mirza. If norovirus infection is suspected, PPE use is recommended for individuals in the patient care area, she added. 

Although state, local, and territorial health departments are not required to report individual cases of norovirus to the CDC, healthcare providers are encouraged to report all outbreaks of acute gastroenteritis, including suspected outbreaks of norovirus, to the appropriate state, local, or territorial health department, said Mirza. “Health departments are encouraged to report all suspected and confirmed norovirus outbreaks through the National Outbreak Reporting System and CaliciNet,” she added.

“Infection control measures, such as thorough hand washing, cleaning and disinfecting surfaces with bleach, and patient isolation and contact precautions in congregate or healthcare settings are the best ways to prevent norovirus and keep it from spreading to others,” Mirza said.

Remind patients that alcohol-based hand sanitizer is ineffective against norovirus, because the virus’s protective protein shell prevents the alcohol from penetrating and inactivating the virus, Mirza emphasized. “Soap and water work to remove germs from hands,” she said.

 

Cruise Ship Considerations

Cruise ships continue to be sources of increased risk for norovirus, according the CDC. The CDC’s Vessel Sanitation Program (VSP) was created to help the cruise industry prevent public health issues such as norovirus outbreaks, and to provide guidance for actions to take in the event of outbreaks. 

For example, the most recently reported outbreak of norovirus on a cruise ship reported to the VSP was January 4, 2025, and occurred on a Holland America cruise from December 30, 2024, through January 8, 2025. Overall, 4.0% of passengers and 1.0% of crew members reported illness. Following VSP guidance, the ship reported increased cleaning and disinfection procedures and the collection of stool specimens for testing, and isolation of ill passengers and crew.

 

Clinical Perspective

In clinical practice, the number of norovirus cases is significantly exceeding previous years, and the trend seems to be consistent nationwide, David J. Cennimo, MD, associate professor of medicine and pediatrics at Rutgers New Jersey Medical School, Newark, New Jersey, said in an interview.

“Norovirus is incredibly contagious and spreads very quickly, which is how you get entire cruise ships infected at once,” he said. Norovirus is notoriously difficult to disinfect or kill, he added.

One possible contributor to the surge in cases is increased travel, especially during the holiday season, when people are coming together and sharing food, Cennimo noted. “We have seen many infections such as pneumonia return to levels approaching the period before the COVID-19 pandemic,” he said. 

For norovirus prevention, strict attention to sanitation and handwashing is a must at home or when traveling, said Cennimo. For clinicians, it is important to report outbreaks of GI illness so appropriate control measures can be taken, he said.

Visit the CDC’s website on norovirus prevention for more information. 

Mirza and Cennimo had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

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Norovirus cases continue to rise in the United States this winter, at levels higher than the same time period in previous years, according to the latest data from the Centers for Disease Control and Prevention (CDC).

Current data from the CDC’s NoroSTAT monitoring system show 495 reported outbreaks during the period from August 1, 2024, to December 11, 2024, compared with 363 outbreaks during the same period last year. In addition, the total number of norovirus outbreaks in the current season are higher than those reported in the seasonal years: 2012-2020 and 2021-2024.

Circulating strains of norovirus change over time, which can affect disease burden and potential disease severity, Sara Mirza, MD, an epidemiologist in the CDC’s Division of Viral Diseases, said in an interview.

The numbers for the 2024 norovirus season (considered approximately November to April) have reached or exceeded the case numbers seen before the COVID-19 pandemic, Mirza said.

The increase in cases may be caused in part by a new predominant strain of norovirus. “For the fall/winter of 2024-2025 season, genogroup 2, genotype 17, known as GII.17, has become the most detected genotype (strain) in the US among laboratory confirmed outbreaks reported to CDC,” said Mirza. “At this time, there is no indication that GII.17 causes more severe illness or affects one population more than another, but we are continuing to conduct surveillance to assess,” she added.

 

Clinical Takeaways

“Norovirus affects all ages, but young children and older adults are most at risk from more severe outcomes,” said Mirza.

“Clinicians treating older patients for acute gastroenteritis should be aware of these elevated risks and be sure to include norovirus as a potentially serious diagnosis, particularly in vulnerable patients with other diseases and those living in congregate settings, such as nursing homes,” she said.

When treating a patient with norovirus during an outbreak, use soap and water for hand hygiene after caring for patients with suspected or confirmed norovirus gastroenteritis, said Mirza. If norovirus infection is suspected, PPE use is recommended for individuals in the patient care area, she added. 

Although state, local, and territorial health departments are not required to report individual cases of norovirus to the CDC, healthcare providers are encouraged to report all outbreaks of acute gastroenteritis, including suspected outbreaks of norovirus, to the appropriate state, local, or territorial health department, said Mirza. “Health departments are encouraged to report all suspected and confirmed norovirus outbreaks through the National Outbreak Reporting System and CaliciNet,” she added.

“Infection control measures, such as thorough hand washing, cleaning and disinfecting surfaces with bleach, and patient isolation and contact precautions in congregate or healthcare settings are the best ways to prevent norovirus and keep it from spreading to others,” Mirza said.

Remind patients that alcohol-based hand sanitizer is ineffective against norovirus, because the virus’s protective protein shell prevents the alcohol from penetrating and inactivating the virus, Mirza emphasized. “Soap and water work to remove germs from hands,” she said.

 

Cruise Ship Considerations

Cruise ships continue to be sources of increased risk for norovirus, according the CDC. The CDC’s Vessel Sanitation Program (VSP) was created to help the cruise industry prevent public health issues such as norovirus outbreaks, and to provide guidance for actions to take in the event of outbreaks. 

For example, the most recently reported outbreak of norovirus on a cruise ship reported to the VSP was January 4, 2025, and occurred on a Holland America cruise from December 30, 2024, through January 8, 2025. Overall, 4.0% of passengers and 1.0% of crew members reported illness. Following VSP guidance, the ship reported increased cleaning and disinfection procedures and the collection of stool specimens for testing, and isolation of ill passengers and crew.

 

Clinical Perspective

In clinical practice, the number of norovirus cases is significantly exceeding previous years, and the trend seems to be consistent nationwide, David J. Cennimo, MD, associate professor of medicine and pediatrics at Rutgers New Jersey Medical School, Newark, New Jersey, said in an interview.

“Norovirus is incredibly contagious and spreads very quickly, which is how you get entire cruise ships infected at once,” he said. Norovirus is notoriously difficult to disinfect or kill, he added.

One possible contributor to the surge in cases is increased travel, especially during the holiday season, when people are coming together and sharing food, Cennimo noted. “We have seen many infections such as pneumonia return to levels approaching the period before the COVID-19 pandemic,” he said. 

For norovirus prevention, strict attention to sanitation and handwashing is a must at home or when traveling, said Cennimo. For clinicians, it is important to report outbreaks of GI illness so appropriate control measures can be taken, he said.

Visit the CDC’s website on norovirus prevention for more information. 

Mirza and Cennimo had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

Norovirus cases continue to rise in the United States this winter, at levels higher than the same time period in previous years, according to the latest data from the Centers for Disease Control and Prevention (CDC).

Current data from the CDC’s NoroSTAT monitoring system show 495 reported outbreaks during the period from August 1, 2024, to December 11, 2024, compared with 363 outbreaks during the same period last year. In addition, the total number of norovirus outbreaks in the current season are higher than those reported in the seasonal years: 2012-2020 and 2021-2024.

Circulating strains of norovirus change over time, which can affect disease burden and potential disease severity, Sara Mirza, MD, an epidemiologist in the CDC’s Division of Viral Diseases, said in an interview.

The numbers for the 2024 norovirus season (considered approximately November to April) have reached or exceeded the case numbers seen before the COVID-19 pandemic, Mirza said.

The increase in cases may be caused in part by a new predominant strain of norovirus. “For the fall/winter of 2024-2025 season, genogroup 2, genotype 17, known as GII.17, has become the most detected genotype (strain) in the US among laboratory confirmed outbreaks reported to CDC,” said Mirza. “At this time, there is no indication that GII.17 causes more severe illness or affects one population more than another, but we are continuing to conduct surveillance to assess,” she added.

 

Clinical Takeaways

“Norovirus affects all ages, but young children and older adults are most at risk from more severe outcomes,” said Mirza.

“Clinicians treating older patients for acute gastroenteritis should be aware of these elevated risks and be sure to include norovirus as a potentially serious diagnosis, particularly in vulnerable patients with other diseases and those living in congregate settings, such as nursing homes,” she said.

When treating a patient with norovirus during an outbreak, use soap and water for hand hygiene after caring for patients with suspected or confirmed norovirus gastroenteritis, said Mirza. If norovirus infection is suspected, PPE use is recommended for individuals in the patient care area, she added. 

Although state, local, and territorial health departments are not required to report individual cases of norovirus to the CDC, healthcare providers are encouraged to report all outbreaks of acute gastroenteritis, including suspected outbreaks of norovirus, to the appropriate state, local, or territorial health department, said Mirza. “Health departments are encouraged to report all suspected and confirmed norovirus outbreaks through the National Outbreak Reporting System and CaliciNet,” she added.

“Infection control measures, such as thorough hand washing, cleaning and disinfecting surfaces with bleach, and patient isolation and contact precautions in congregate or healthcare settings are the best ways to prevent norovirus and keep it from spreading to others,” Mirza said.

Remind patients that alcohol-based hand sanitizer is ineffective against norovirus, because the virus’s protective protein shell prevents the alcohol from penetrating and inactivating the virus, Mirza emphasized. “Soap and water work to remove germs from hands,” she said.

 

Cruise Ship Considerations

Cruise ships continue to be sources of increased risk for norovirus, according the CDC. The CDC’s Vessel Sanitation Program (VSP) was created to help the cruise industry prevent public health issues such as norovirus outbreaks, and to provide guidance for actions to take in the event of outbreaks. 

For example, the most recently reported outbreak of norovirus on a cruise ship reported to the VSP was January 4, 2025, and occurred on a Holland America cruise from December 30, 2024, through January 8, 2025. Overall, 4.0% of passengers and 1.0% of crew members reported illness. Following VSP guidance, the ship reported increased cleaning and disinfection procedures and the collection of stool specimens for testing, and isolation of ill passengers and crew.

 

Clinical Perspective

In clinical practice, the number of norovirus cases is significantly exceeding previous years, and the trend seems to be consistent nationwide, David J. Cennimo, MD, associate professor of medicine and pediatrics at Rutgers New Jersey Medical School, Newark, New Jersey, said in an interview.

“Norovirus is incredibly contagious and spreads very quickly, which is how you get entire cruise ships infected at once,” he said. Norovirus is notoriously difficult to disinfect or kill, he added.

One possible contributor to the surge in cases is increased travel, especially during the holiday season, when people are coming together and sharing food, Cennimo noted. “We have seen many infections such as pneumonia return to levels approaching the period before the COVID-19 pandemic,” he said. 

For norovirus prevention, strict attention to sanitation and handwashing is a must at home or when traveling, said Cennimo. For clinicians, it is important to report outbreaks of GI illness so appropriate control measures can be taken, he said.

Visit the CDC’s website on norovirus prevention for more information. 

Mirza and Cennimo had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

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Red Wine May Not Be a Health Tonic, But Is It a Cancer Risk?

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Mon, 01/13/2025 - 16:54

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

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The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

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Are Patients On GLP-1s Getting the Right Nutrients?

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As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, said in an interview. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.” 

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

 

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs said in an interview.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta, Georgia. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

 

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in The International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

 

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

 

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized.”

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies 

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

 

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietitian.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dietitians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and questions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

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As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, said in an interview. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.” 

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

 

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs said in an interview.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta, Georgia. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

 

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in The International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

 

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

 

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized.”

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies 

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

 

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietitian.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dietitians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and questions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, said in an interview. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.” 

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

 

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs said in an interview.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta, Georgia. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

 

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in The International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

 

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

 

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized.”

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies 

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

 

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietitian.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dietitians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and questions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

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