Digestive Health

The US Food and Drug Administration (FDA) has approved the subcutaneous administration of vedolizumab (Entyvio) for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) vedolizumab. 

The move follows the FDA’s approval last year of subcutaneous vedolizumab for maintenance treatment of adults with moderately to severely active ulcerative colitis (UC). 

The humanized immunoglobulin G1 monoclonal antibody is available as a single-dose prefilled pen (Entyvio Pen).

The FDA first approved the IV formulation of the biologic in 2014 for patients with moderate to severe UC and CD who cannot tolerate other therapies or in whom such therapies have failed. 

The approval of subcutaneous vedolizumab for maintenance treatment of CD is based on the phase 3, randomized, double-blind, placebo-controlled VISIBLE 2 trial.

The trial enrolled 409 adult patients with moderately to severely active CD who had clinical response at week 6 following two doses of open-label IV vedolizumab at weeks 0 and 2. 

At week 6, they were randomly allocated in a 2:1 ratio to receive vedolizumab 108 mg administered by subcutaneous injection or placebo every 2 weeks. The primary endpoint was clinical remission at week 52, which was defined as a total Crohn’s Disease Activity Index score ≤ 150.

The results showed that significantly more patients receiving subcutaneous vedolizumab than placebo achieved long-term clinical remission (48% vs 34%; P < .01), the company said in a news release. 

The safety profile of subcutaneous vedolizumab is generally consistent with the known safety profile of IV vedolizumab, with the addition of injection-site reactions (including injection-site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria, and edema).

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission,” Timothy Ritter, MD, senior medical director, GI Alliance Research, and assistant professor of medicine, Burnett School of Medicine at TCU, Fort Worth, Texas, said in the news release.

GI Alliance

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the subcutaneous administration of vedolizumab (Entyvio) for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) vedolizumab. 

The move follows the FDA’s approval last year of subcutaneous vedolizumab for maintenance treatment of adults with moderately to severely active ulcerative colitis (UC). 

The humanized immunoglobulin G1 monoclonal antibody is available as a single-dose prefilled pen (Entyvio Pen).

The FDA first approved the IV formulation of the biologic in 2014 for patients with moderate to severe UC and CD who cannot tolerate other therapies or in whom such therapies have failed. 

The approval of subcutaneous vedolizumab for maintenance treatment of CD is based on the phase 3, randomized, double-blind, placebo-controlled VISIBLE 2 trial.

The trial enrolled 409 adult patients with moderately to severely active CD who had clinical response at week 6 following two doses of open-label IV vedolizumab at weeks 0 and 2. 

At week 6, they were randomly allocated in a 2:1 ratio to receive vedolizumab 108 mg administered by subcutaneous injection or placebo every 2 weeks. The primary endpoint was clinical remission at week 52, which was defined as a total Crohn’s Disease Activity Index score ≤ 150.

The results showed that significantly more patients receiving subcutaneous vedolizumab than placebo achieved long-term clinical remission (48% vs 34%; P < .01), the company said in a news release. 

The safety profile of subcutaneous vedolizumab is generally consistent with the known safety profile of IV vedolizumab, with the addition of injection-site reactions (including injection-site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria, and edema).

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission,” Timothy Ritter, MD, senior medical director, GI Alliance Research, and assistant professor of medicine, Burnett School of Medicine at TCU, Fort Worth, Texas, said in the news release.

GI Alliance

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the subcutaneous administration of vedolizumab (Entyvio) for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) vedolizumab. 

The move follows the FDA’s approval last year of subcutaneous vedolizumab for maintenance treatment of adults with moderately to severely active ulcerative colitis (UC). 

The humanized immunoglobulin G1 monoclonal antibody is available as a single-dose prefilled pen (Entyvio Pen).

The FDA first approved the IV formulation of the biologic in 2014 for patients with moderate to severe UC and CD who cannot tolerate other therapies or in whom such therapies have failed. 

The approval of subcutaneous vedolizumab for maintenance treatment of CD is based on the phase 3, randomized, double-blind, placebo-controlled VISIBLE 2 trial.

The trial enrolled 409 adult patients with moderately to severely active CD who had clinical response at week 6 following two doses of open-label IV vedolizumab at weeks 0 and 2. 

At week 6, they were randomly allocated in a 2:1 ratio to receive vedolizumab 108 mg administered by subcutaneous injection or placebo every 2 weeks. The primary endpoint was clinical remission at week 52, which was defined as a total Crohn’s Disease Activity Index score ≤ 150.

The results showed that significantly more patients receiving subcutaneous vedolizumab than placebo achieved long-term clinical remission (48% vs 34%; P < .01), the company said in a news release. 

The safety profile of subcutaneous vedolizumab is generally consistent with the known safety profile of IV vedolizumab, with the addition of injection-site reactions (including injection-site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria, and edema).

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission,” Timothy Ritter, MD, senior medical director, GI Alliance Research, and assistant professor of medicine, Burnett School of Medicine at TCU, Fort Worth, Texas, said in the news release.

GI Alliance

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

LONDON — Weight loss, glycemic control, fatty liver, and the need for insulin all showed improvement in patients with both refractory type 2 diabetes and obesity after a gut liner known as EndoBarrier (RESET, Morphic Medical, United States) was implanted for 1 year, showed data.

Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.

Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.

“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.

Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
 

Convenient, Reversible Procedure

Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.

Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.

The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.

“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.

Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
 

Over Half Maintained Full Improvement 2 Years Post Removal

A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m², and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.

Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.

Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m², A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.

Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).

Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.

Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.

Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.

Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”

Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.

EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m².
 

A version of this article appeared on Medscape.com.

TOPLINE:

Being positive for Helicobacter pylori is associated with a higher risk for colorectal cancer (CRC) incidence and CRC mortality, new data show; however, a 2-week course of antibiotics to eliminate the bacterial infection can reduce the risk of developing and dying from CRC.

METHODOLOGY:

• H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
• Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
• To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
• Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.

TAKEAWAY:

• H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
• Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
• Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
• Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.

IN PRACTICE:

“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”

SOURCE:

The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.

LIMITATIONS:

The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.

DISCLOSURES:

The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Being positive for Helicobacter pylori is associated with a higher risk for colorectal cancer (CRC) incidence and CRC mortality, new data show; however, a 2-week course of antibiotics to eliminate the bacterial infection can reduce the risk of developing and dying from CRC.

METHODOLOGY:

• H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
• Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
• To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
• Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.

TAKEAWAY:

• H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
• Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
• Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
• Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.

IN PRACTICE:

“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”

SOURCE:

The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.

LIMITATIONS:

The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.

DISCLOSURES:

The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Being positive for Helicobacter pylori is associated with a higher risk for colorectal cancer (CRC) incidence and CRC mortality, new data show; however, a 2-week course of antibiotics to eliminate the bacterial infection can reduce the risk of developing and dying from CRC.

METHODOLOGY:

• H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
• Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
• To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
• Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.

TAKEAWAY:

• H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
• Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
• Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
• Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.

IN PRACTICE:

“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”

SOURCE:

The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.

LIMITATIONS:

The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.

DISCLOSURES:

The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.

A version of this article appeared on Medscape.com.

Erosive esophagitis (EE) is erosion of the esophageal epithelium due to chronic irritation. It can be caused by a number of factors but is primarily a result of gastroesophageal reflux disease (GERD). The main symptoms of EE are heartburn and regurgitation; other symptoms can include epigastric pain, odynophagia, dysphagia, nausea, chronic cough, dental erosion, laryngitis, and asthma. Symptoms can be exacerbated by eating certain trigger foods or when lying down. Diagnosis requires testing to differentiate EE from other manifestations of GERD, including nonerosive esophagitis and Barrett esophagus (BE). EE occurs in approximately 30% of cases of GERD, and EE may evolve to BE in 1%-13% of cases.

Long-term management of EE focuses on relieving symptoms to allow the esophageal lining to heal, thereby reducing both acute symptoms and the risk for other complications. Management plans may incorporate lifestyle changes, such as dietary modifications and weight loss, alongside pharmacologic therapy. In extreme cases, surgery may be considered to repair a damaged esophagus and/or to prevent ongoing acid reflux. If left untreated, EE may progress, potentially leading to more serious conditions.

Here are five things to know about EE.

1. GERD is the main risk factor for EE, but not the only risk factor.

An estimated 1% of the population has EE. Risk factors other than GERD include:

Radiation therapy toxicity can cause acute or chronic EE. For individuals undergoing radiotherapy, radiation esophagitis is a relatively frequent complication. Acute esophagitis generally occurs in all patients taking radiation doses of 6000 cGy given in fractions of 1000 cGy per week. The risk is lower among patients on longer schedules and lower doses of radiotherapy.

Bacterial, viral, and fungal infections can cause EE. These include herpes, CMV, HIV, Helicobacter pylori, and Candida.

Food allergies, asthma, and eczema are associated with eosinophilic esophagitis, which disproportionately affects young men and has an estimated prevalence of 55 cases per 100,000 population.

Oral medication in pill form causes esophagitis at an estimated rate of 3.9 cases per 100,000 population per year. The mean age at diagnosis is 41.5 years. Oral bisphosphonates such as alendronate are the most common agents, along with antibiotics such as tetracycline, doxycycline, and clindamycin. There have also been reports of pill-induced esophagitis with NSAIDs, aspirin, ferrous sulfate, potassium chloride, and mexiletine.

Excessive vomiting can, in rare cases, cause esophagitis.

Certain autoimmune diseases can manifest as EE.

2. Proton pump inhibitors (PPIs) remain the preferred treatment for EE.

Several over-the-counter and prescription medications can be used to manage the symptoms of EE. PPIs are the preferred treatment both in the acute setting and for maintenance therapy. PPIs help to alleviate symptoms and promote healing of the esophageal lining by reducing the production of stomach acid. Options include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. Many patients with EE require a dose that exceeds the FDA-approved dose for GERD. For instance, a 40-mg/d dosage of omeprazole is recommended in the latest guidelines, although the FDA-approved dosage is 20 mg/d.

H2-receptor antagonists, including famotidine, cimetidine, and nizatidine, may also be prescribed to reduce stomach acid production and promote healing in patients with EE due to GERD, but these agents are considered less efficacious than PPIs for either acute or maintenance therapy.

The potassium-competitive acid blocker (PCAB) vonoprazan is the latest agent to be indicated for EE and may provide more potent acid suppression for patients. A randomized comparative trial showed noninferiority compared with lansoprazole for healing and maintenance of healing of EE. In another randomized comparative study, the investigational PCAP fexuprazan was shown to be noninferior to the PPI esomeprazole in treating EE.

Mild GERD symptoms can be controlled by traditional antacids taken after each meal and at bedtime or with short-term use of prokinetic agents, which can help reduce acid reflux by improving esophageal and stomach motility and by increasing pressure to the lower esophageal sphincter. Gastric emptying is also accelerated by prokinetic agents. Long-term use is discouraged, as it may cause serious or life-threatening complications.

In patients who do not fully respond to PPI therapy, surgical therapy may be considered. Other candidates for surgery include younger patients, those who have difficulty adhering to treatment, postmenopausal women with osteoporosis, patients with cardiac conduction defects, and those for whom the cost of treatment is prohibitive. Surgery may also be warranted if there are extraesophageal manifestations of GERD, such as enamel erosion; respiratory issues (eg, coughing, wheezing, aspiration); or ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media). For those who have progressed to BE, surgical intervention is also indicated.

The types of surgery for patients with EE have evolved to include both transthoracic and transabdominal fundoplication. Usually, a 360° transabdominal fundoplication is performed. General anesthesia is required for laparoscopic fundoplication, in which five small incisions are used to create a new valve at the level of the esophagogastric junction by wrapping the fundus of the stomach around the esophagus.

Laparoscopic insertion of a small band known as the LINX Reflux Management System is FDA approved to augment the lower esophageal sphincter. The system creates a natural barrier to reflux by placing a band consisting of titanium beads with magnetic cores around the esophagus just above the stomach. The magnetic bond is temporarily disrupted by swallowing, allowing food and liquid to pass.

Endoscopic therapies are another treatment option for certain patients who are not considered candidates for surgery or long-term therapy. Among the types of endoscopic procedures are radiofrequency therapy, suturing/plication, and mucosal ablation/resection techniques at the gastroesophageal junction. Full-thickness endoscopic suturing is an area of interest because this technique offers significant durability of the recreated lower esophageal sphincter.

3. PPI therapy for GERD should be stopped before endoscopy is performed to confirm a diagnosis of EE.

A clinical diagnosis of GERD can be made if the presenting symptoms are heartburn and regurgitation, without chest pain or alarm symptoms such as dysphagia, weight loss, or gastrointestinal bleeding. In this setting, once-daily PPIs are generally prescribed for 8 weeks to see if symptoms resolve. If symptoms have not resolved, a twice-daily PPI regimen may be prescribed. In patients who do not respond to PPIs, or for whom GERD returns after stopping therapy, an upper endoscopy with biopsy is recommended after 2-4 weeks off therapy to rule out other causes. Endoscopy should be the first step in diagnosis for individuals experiencing chest pain without heartburn; those in whom heart disease has been ruled out; individuals experiencing dysphagia, weight loss, or gastrointestinal bleeding; or those who have multiple risk factors for BE.

4. The most serious complication of EE is BE, which can lead to esophageal cancer.

Several complications can arise from EE. The most serious of these is BE, which can lead to esophageal adenocarcinoma. BE is characterized by the conversion of normal distal squamous esophageal epithelium to columnar epithelium. It has the potential to become malignant if it exhibits intestinal-type metaplasia. In the industrialized world, adenocarcinoma currently represents more than half of all esophageal cancers. The most common symptom of esophageal cancer is dysphagia. Other signs and symptoms include weight loss, hoarseness, chronic or intractable cough, bleeding, epigastric or retrosternal pain, frequent pneumonia, and, if metastatic, bone pain.

5. Lifestyle modifications can help control the symptoms of EE.

Guidelines recommend a number of lifestyle modification strategies to help control the symptoms of EE. Smoking cessation and weight loss are two evidence-based strategies for relieving symptoms of GERD and, ultimately, lowering the risk for esophageal cancer. One large prospective Norwegian cohort study (N = 29,610) found that stopping smoking improved GERD symptoms, but only in those with normal body mass index. In a smaller Japanese study (N = 191) specifically surveying people attempting smoking cessation, individuals who successfully stopped smoking had a 44% improvement in GERD symptoms at 1 year, vs an 18% improvement in those who continued to smoke, with no statistical difference between the success and failure groups based on patient body mass index (P = .60).

Other recommended strategies for nonpharmacologic management of EE symptoms include elevation of the head when lying down in bed and avoidance of lying down after eating, cessation of alcohol consumption, avoidance of food close to bedtime, and avoidance of trigger foods that can incite or worsen symptoms of acid reflux. Such trigger foods vary among individuals, but they often include fatty foods, coffee, chocolate, carbonated beverages, spicy foods, citrus fruits, and tomatoes.

Dr. Puerta has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Erosive esophagitis (EE) is erosion of the esophageal epithelium due to chronic irritation. It can be caused by a number of factors but is primarily a result of gastroesophageal reflux disease (GERD). The main symptoms of EE are heartburn and regurgitation; other symptoms can include epigastric pain, odynophagia, dysphagia, nausea, chronic cough, dental erosion, laryngitis, and asthma. Symptoms can be exacerbated by eating certain trigger foods or when lying down. Diagnosis requires testing to differentiate EE from other manifestations of GERD, including nonerosive esophagitis and Barrett esophagus (BE). EE occurs in approximately 30% of cases of GERD, and EE may evolve to BE in 1%-13% of cases.

Long-term management of EE focuses on relieving symptoms to allow the esophageal lining to heal, thereby reducing both acute symptoms and the risk for other complications. Management plans may incorporate lifestyle changes, such as dietary modifications and weight loss, alongside pharmacologic therapy. In extreme cases, surgery may be considered to repair a damaged esophagus and/or to prevent ongoing acid reflux. If left untreated, EE may progress, potentially leading to more serious conditions.

Here are five things to know about EE.

1. GERD is the main risk factor for EE, but not the only risk factor.

An estimated 1% of the population has EE. Risk factors other than GERD include:

Radiation therapy toxicity can cause acute or chronic EE. For individuals undergoing radiotherapy, radiation esophagitis is a relatively frequent complication. Acute esophagitis generally occurs in all patients taking radiation doses of 6000 cGy given in fractions of 1000 cGy per week. The risk is lower among patients on longer schedules and lower doses of radiotherapy.

Bacterial, viral, and fungal infections can cause EE. These include herpes, CMV, HIV, Helicobacter pylori, and Candida.

Food allergies, asthma, and eczema are associated with eosinophilic esophagitis, which disproportionately affects young men and has an estimated prevalence of 55 cases per 100,000 population.

Oral medication in pill form causes esophagitis at an estimated rate of 3.9 cases per 100,000 population per year. The mean age at diagnosis is 41.5 years. Oral bisphosphonates such as alendronate are the most common agents, along with antibiotics such as tetracycline, doxycycline, and clindamycin. There have also been reports of pill-induced esophagitis with NSAIDs, aspirin, ferrous sulfate, potassium chloride, and mexiletine.

Excessive vomiting can, in rare cases, cause esophagitis.

Certain autoimmune diseases can manifest as EE.

2. Proton pump inhibitors (PPIs) remain the preferred treatment for EE.

Several over-the-counter and prescription medications can be used to manage the symptoms of EE. PPIs are the preferred treatment both in the acute setting and for maintenance therapy. PPIs help to alleviate symptoms and promote healing of the esophageal lining by reducing the production of stomach acid. Options include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. Many patients with EE require a dose that exceeds the FDA-approved dose for GERD. For instance, a 40-mg/d dosage of omeprazole is recommended in the latest guidelines, although the FDA-approved dosage is 20 mg/d.

H2-receptor antagonists, including famotidine, cimetidine, and nizatidine, may also be prescribed to reduce stomach acid production and promote healing in patients with EE due to GERD, but these agents are considered less efficacious than PPIs for either acute or maintenance therapy.

The potassium-competitive acid blocker (PCAB) vonoprazan is the latest agent to be indicated for EE and may provide more potent acid suppression for patients. A randomized comparative trial showed noninferiority compared with lansoprazole for healing and maintenance of healing of EE. In another randomized comparative study, the investigational PCAP fexuprazan was shown to be noninferior to the PPI esomeprazole in treating EE.

Mild GERD symptoms can be controlled by traditional antacids taken after each meal and at bedtime or with short-term use of prokinetic agents, which can help reduce acid reflux by improving esophageal and stomach motility and by increasing pressure to the lower esophageal sphincter. Gastric emptying is also accelerated by prokinetic agents. Long-term use is discouraged, as it may cause serious or life-threatening complications.

In patients who do not fully respond to PPI therapy, surgical therapy may be considered. Other candidates for surgery include younger patients, those who have difficulty adhering to treatment, postmenopausal women with osteoporosis, patients with cardiac conduction defects, and those for whom the cost of treatment is prohibitive. Surgery may also be warranted if there are extraesophageal manifestations of GERD, such as enamel erosion; respiratory issues (eg, coughing, wheezing, aspiration); or ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media). For those who have progressed to BE, surgical intervention is also indicated.

The types of surgery for patients with EE have evolved to include both transthoracic and transabdominal fundoplication. Usually, a 360° transabdominal fundoplication is performed. General anesthesia is required for laparoscopic fundoplication, in which five small incisions are used to create a new valve at the level of the esophagogastric junction by wrapping the fundus of the stomach around the esophagus.

Laparoscopic insertion of a small band known as the LINX Reflux Management System is FDA approved to augment the lower esophageal sphincter. The system creates a natural barrier to reflux by placing a band consisting of titanium beads with magnetic cores around the esophagus just above the stomach. The magnetic bond is temporarily disrupted by swallowing, allowing food and liquid to pass.

Endoscopic therapies are another treatment option for certain patients who are not considered candidates for surgery or long-term therapy. Among the types of endoscopic procedures are radiofrequency therapy, suturing/plication, and mucosal ablation/resection techniques at the gastroesophageal junction. Full-thickness endoscopic suturing is an area of interest because this technique offers significant durability of the recreated lower esophageal sphincter.

3. PPI therapy for GERD should be stopped before endoscopy is performed to confirm a diagnosis of EE.

A clinical diagnosis of GERD can be made if the presenting symptoms are heartburn and regurgitation, without chest pain or alarm symptoms such as dysphagia, weight loss, or gastrointestinal bleeding. In this setting, once-daily PPIs are generally prescribed for 8 weeks to see if symptoms resolve. If symptoms have not resolved, a twice-daily PPI regimen may be prescribed. In patients who do not respond to PPIs, or for whom GERD returns after stopping therapy, an upper endoscopy with biopsy is recommended after 2-4 weeks off therapy to rule out other causes. Endoscopy should be the first step in diagnosis for individuals experiencing chest pain without heartburn; those in whom heart disease has been ruled out; individuals experiencing dysphagia, weight loss, or gastrointestinal bleeding; or those who have multiple risk factors for BE.

4. The most serious complication of EE is BE, which can lead to esophageal cancer.

Several complications can arise from EE. The most serious of these is BE, which can lead to esophageal adenocarcinoma. BE is characterized by the conversion of normal distal squamous esophageal epithelium to columnar epithelium. It has the potential to become malignant if it exhibits intestinal-type metaplasia. In the industrialized world, adenocarcinoma currently represents more than half of all esophageal cancers. The most common symptom of esophageal cancer is dysphagia. Other signs and symptoms include weight loss, hoarseness, chronic or intractable cough, bleeding, epigastric or retrosternal pain, frequent pneumonia, and, if metastatic, bone pain.

5. Lifestyle modifications can help control the symptoms of EE.

Guidelines recommend a number of lifestyle modification strategies to help control the symptoms of EE. Smoking cessation and weight loss are two evidence-based strategies for relieving symptoms of GERD and, ultimately, lowering the risk for esophageal cancer. One large prospective Norwegian cohort study (N = 29,610) found that stopping smoking improved GERD symptoms, but only in those with normal body mass index. In a smaller Japanese study (N = 191) specifically surveying people attempting smoking cessation, individuals who successfully stopped smoking had a 44% improvement in GERD symptoms at 1 year, vs an 18% improvement in those who continued to smoke, with no statistical difference between the success and failure groups based on patient body mass index (P = .60).

Other recommended strategies for nonpharmacologic management of EE symptoms include elevation of the head when lying down in bed and avoidance of lying down after eating, cessation of alcohol consumption, avoidance of food close to bedtime, and avoidance of trigger foods that can incite or worsen symptoms of acid reflux. Such trigger foods vary among individuals, but they often include fatty foods, coffee, chocolate, carbonated beverages, spicy foods, citrus fruits, and tomatoes.

Dr. Puerta has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Erosive esophagitis (EE) is erosion of the esophageal epithelium due to chronic irritation. It can be caused by a number of factors but is primarily a result of gastroesophageal reflux disease (GERD). The main symptoms of EE are heartburn and regurgitation; other symptoms can include epigastric pain, odynophagia, dysphagia, nausea, chronic cough, dental erosion, laryngitis, and asthma. Symptoms can be exacerbated by eating certain trigger foods or when lying down. Diagnosis requires testing to differentiate EE from other manifestations of GERD, including nonerosive esophagitis and Barrett esophagus (BE). EE occurs in approximately 30% of cases of GERD, and EE may evolve to BE in 1%-13% of cases.

Long-term management of EE focuses on relieving symptoms to allow the esophageal lining to heal, thereby reducing both acute symptoms and the risk for other complications. Management plans may incorporate lifestyle changes, such as dietary modifications and weight loss, alongside pharmacologic therapy. In extreme cases, surgery may be considered to repair a damaged esophagus and/or to prevent ongoing acid reflux. If left untreated, EE may progress, potentially leading to more serious conditions.

Here are five things to know about EE.

1. GERD is the main risk factor for EE, but not the only risk factor.

An estimated 1% of the population has EE. Risk factors other than GERD include:

Radiation therapy toxicity can cause acute or chronic EE. For individuals undergoing radiotherapy, radiation esophagitis is a relatively frequent complication. Acute esophagitis generally occurs in all patients taking radiation doses of 6000 cGy given in fractions of 1000 cGy per week. The risk is lower among patients on longer schedules and lower doses of radiotherapy.

Bacterial, viral, and fungal infections can cause EE. These include herpes, CMV, HIV, Helicobacter pylori, and Candida.

Food allergies, asthma, and eczema are associated with eosinophilic esophagitis, which disproportionately affects young men and has an estimated prevalence of 55 cases per 100,000 population.

Oral medication in pill form causes esophagitis at an estimated rate of 3.9 cases per 100,000 population per year. The mean age at diagnosis is 41.5 years. Oral bisphosphonates such as alendronate are the most common agents, along with antibiotics such as tetracycline, doxycycline, and clindamycin. There have also been reports of pill-induced esophagitis with NSAIDs, aspirin, ferrous sulfate, potassium chloride, and mexiletine.

Excessive vomiting can, in rare cases, cause esophagitis.

Certain autoimmune diseases can manifest as EE.

2. Proton pump inhibitors (PPIs) remain the preferred treatment for EE.

Several over-the-counter and prescription medications can be used to manage the symptoms of EE. PPIs are the preferred treatment both in the acute setting and for maintenance therapy. PPIs help to alleviate symptoms and promote healing of the esophageal lining by reducing the production of stomach acid. Options include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. Many patients with EE require a dose that exceeds the FDA-approved dose for GERD. For instance, a 40-mg/d dosage of omeprazole is recommended in the latest guidelines, although the FDA-approved dosage is 20 mg/d.

H2-receptor antagonists, including famotidine, cimetidine, and nizatidine, may also be prescribed to reduce stomach acid production and promote healing in patients with EE due to GERD, but these agents are considered less efficacious than PPIs for either acute or maintenance therapy.

The potassium-competitive acid blocker (PCAB) vonoprazan is the latest agent to be indicated for EE and may provide more potent acid suppression for patients. A randomized comparative trial showed noninferiority compared with lansoprazole for healing and maintenance of healing of EE. In another randomized comparative study, the investigational PCAP fexuprazan was shown to be noninferior to the PPI esomeprazole in treating EE.

Mild GERD symptoms can be controlled by traditional antacids taken after each meal and at bedtime or with short-term use of prokinetic agents, which can help reduce acid reflux by improving esophageal and stomach motility and by increasing pressure to the lower esophageal sphincter. Gastric emptying is also accelerated by prokinetic agents. Long-term use is discouraged, as it may cause serious or life-threatening complications.

In patients who do not fully respond to PPI therapy, surgical therapy may be considered. Other candidates for surgery include younger patients, those who have difficulty adhering to treatment, postmenopausal women with osteoporosis, patients with cardiac conduction defects, and those for whom the cost of treatment is prohibitive. Surgery may also be warranted if there are extraesophageal manifestations of GERD, such as enamel erosion; respiratory issues (eg, coughing, wheezing, aspiration); or ear, nose, and throat manifestations (eg, hoarseness, sore throat, otitis media). For those who have progressed to BE, surgical intervention is also indicated.

The types of surgery for patients with EE have evolved to include both transthoracic and transabdominal fundoplication. Usually, a 360° transabdominal fundoplication is performed. General anesthesia is required for laparoscopic fundoplication, in which five small incisions are used to create a new valve at the level of the esophagogastric junction by wrapping the fundus of the stomach around the esophagus.

Laparoscopic insertion of a small band known as the LINX Reflux Management System is FDA approved to augment the lower esophageal sphincter. The system creates a natural barrier to reflux by placing a band consisting of titanium beads with magnetic cores around the esophagus just above the stomach. The magnetic bond is temporarily disrupted by swallowing, allowing food and liquid to pass.

Endoscopic therapies are another treatment option for certain patients who are not considered candidates for surgery or long-term therapy. Among the types of endoscopic procedures are radiofrequency therapy, suturing/plication, and mucosal ablation/resection techniques at the gastroesophageal junction. Full-thickness endoscopic suturing is an area of interest because this technique offers significant durability of the recreated lower esophageal sphincter.

3. PPI therapy for GERD should be stopped before endoscopy is performed to confirm a diagnosis of EE.

A clinical diagnosis of GERD can be made if the presenting symptoms are heartburn and regurgitation, without chest pain or alarm symptoms such as dysphagia, weight loss, or gastrointestinal bleeding. In this setting, once-daily PPIs are generally prescribed for 8 weeks to see if symptoms resolve. If symptoms have not resolved, a twice-daily PPI regimen may be prescribed. In patients who do not respond to PPIs, or for whom GERD returns after stopping therapy, an upper endoscopy with biopsy is recommended after 2-4 weeks off therapy to rule out other causes. Endoscopy should be the first step in diagnosis for individuals experiencing chest pain without heartburn; those in whom heart disease has been ruled out; individuals experiencing dysphagia, weight loss, or gastrointestinal bleeding; or those who have multiple risk factors for BE.

4. The most serious complication of EE is BE, which can lead to esophageal cancer.

Several complications can arise from EE. The most serious of these is BE, which can lead to esophageal adenocarcinoma. BE is characterized by the conversion of normal distal squamous esophageal epithelium to columnar epithelium. It has the potential to become malignant if it exhibits intestinal-type metaplasia. In the industrialized world, adenocarcinoma currently represents more than half of all esophageal cancers. The most common symptom of esophageal cancer is dysphagia. Other signs and symptoms include weight loss, hoarseness, chronic or intractable cough, bleeding, epigastric or retrosternal pain, frequent pneumonia, and, if metastatic, bone pain.

5. Lifestyle modifications can help control the symptoms of EE.

Guidelines recommend a number of lifestyle modification strategies to help control the symptoms of EE. Smoking cessation and weight loss are two evidence-based strategies for relieving symptoms of GERD and, ultimately, lowering the risk for esophageal cancer. One large prospective Norwegian cohort study (N = 29,610) found that stopping smoking improved GERD symptoms, but only in those with normal body mass index. In a smaller Japanese study (N = 191) specifically surveying people attempting smoking cessation, individuals who successfully stopped smoking had a 44% improvement in GERD symptoms at 1 year, vs an 18% improvement in those who continued to smoke, with no statistical difference between the success and failure groups based on patient body mass index (P = .60).

Other recommended strategies for nonpharmacologic management of EE symptoms include elevation of the head when lying down in bed and avoidance of lying down after eating, cessation of alcohol consumption, avoidance of food close to bedtime, and avoidance of trigger foods that can incite or worsen symptoms of acid reflux. Such trigger foods vary among individuals, but they often include fatty foods, coffee, chocolate, carbonated beverages, spicy foods, citrus fruits, and tomatoes.

Dr. Puerta has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A fiber supplement also found in beans and other foods may lead to weight loss and improved insulin sensitivity in people with excess body weight, partly due to changes in the gut microbiota.

METHODOLOGY:

• In animal studies, resistant starch (RS), a kind of dietary fiber, has shown a potential to reduce body fat along with other metabolic benefits, but human dietary studies of RS have been inconsistent, especially with a high-fat diet.
• Researchers conducted a crossover, randomized trial to study the effect of RS as a dietary supplement on 37 individuals with overweight or obesity (average age, 33.43 years; 15 women; body mass index > 24 or higher waist circumference).
• Participants were fed a similar background diet and either 40 g of RS (high-amylose maize) or an energy-matched placebo starch daily for 8 weeks and then switched between the two in a separate 8-week period.
• The primary outcome was body weight, and the secondary outcomes were visceral and subcutaneous fat mass, waist circumference, lipid profiles, insulin sensitivity, metabolome, and gut microbiome.
• RS’s impact on gut microbiota composition and function was assessed with metagenomics and metabolomics, and RS-modified gut microbiota’s effect on host body fat and glucose was confirmed by transferring from select average participants to mice.

TAKEAWAY:

• Participants showed a mean weight loss of 2.8 kg after consuming RS for 8 weeks (P < .001), but there was no significant change in body weight in those on placebo starch.
• RS improved insulin sensitivity in people to a greater extent than placebo starch (P = .025) and showed a greater reduction in fat mass, waist circumference, and other obesity-related outcomes.
• The abundance in the gut of the microbe Bifidobacterium adolescentis increased significantly following RS intervention, an increase that exhibited a strong correlation with decreased BMI, suggesting a role of RS in reducing obesity.
• The levels of pro-inflammatory cytokines, such as serum tumor necrosis factor-alpha and interleukin-1 beta, were significantly lower in participants who consumed RS than in those who had placebo starch.

IN PRACTICE:

“Our study provided an effective dietary recommendation using RS as a supplement (40 g/d with a balanced background diet containing 25%-30% fat), which may help to achieve significant weight loss,” the authors wrote.

SOURCE:

This study was led and corresponded by Huating Li, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, and University of Hong Kong, Pok Fu Lam, and published online in Nature Metabolism.

LIMITATIONS:

This study was limited by the small sample size and stringent inclusion criteria for participants. The use of database-driven and taxane-based methodology might have led to difficult-to-classify sequences being discarded and strain-level functional diversity being overlooked. The authors also acknowledged the need to validate the findings of this study in larger and more diverse cohorts.

DISCLOSURES:

This work was supported by the National Key Research and Development Program of China, Shanghai Municipal Key Clinical Specialty, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A fiber supplement also found in beans and other foods may lead to weight loss and improved insulin sensitivity in people with excess body weight, partly due to changes in the gut microbiota.

METHODOLOGY:

• In animal studies, resistant starch (RS), a kind of dietary fiber, has shown a potential to reduce body fat along with other metabolic benefits, but human dietary studies of RS have been inconsistent, especially with a high-fat diet.
• Researchers conducted a crossover, randomized trial to study the effect of RS as a dietary supplement on 37 individuals with overweight or obesity (average age, 33.43 years; 15 women; body mass index > 24 or higher waist circumference).
• Participants were fed a similar background diet and either 40 g of RS (high-amylose maize) or an energy-matched placebo starch daily for 8 weeks and then switched between the two in a separate 8-week period.
• The primary outcome was body weight, and the secondary outcomes were visceral and subcutaneous fat mass, waist circumference, lipid profiles, insulin sensitivity, metabolome, and gut microbiome.
• RS’s impact on gut microbiota composition and function was assessed with metagenomics and metabolomics, and RS-modified gut microbiota’s effect on host body fat and glucose was confirmed by transferring from select average participants to mice.

TAKEAWAY:

• Participants showed a mean weight loss of 2.8 kg after consuming RS for 8 weeks (P < .001), but there was no significant change in body weight in those on placebo starch.
• RS improved insulin sensitivity in people to a greater extent than placebo starch (P = .025) and showed a greater reduction in fat mass, waist circumference, and other obesity-related outcomes.
• The abundance in the gut of the microbe Bifidobacterium adolescentis increased significantly following RS intervention, an increase that exhibited a strong correlation with decreased BMI, suggesting a role of RS in reducing obesity.
• The levels of pro-inflammatory cytokines, such as serum tumor necrosis factor-alpha and interleukin-1 beta, were significantly lower in participants who consumed RS than in those who had placebo starch.

IN PRACTICE:

“Our study provided an effective dietary recommendation using RS as a supplement (40 g/d with a balanced background diet containing 25%-30% fat), which may help to achieve significant weight loss,” the authors wrote.

SOURCE:

This study was led and corresponded by Huating Li, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, and University of Hong Kong, Pok Fu Lam, and published online in Nature Metabolism.

LIMITATIONS:

This study was limited by the small sample size and stringent inclusion criteria for participants. The use of database-driven and taxane-based methodology might have led to difficult-to-classify sequences being discarded and strain-level functional diversity being overlooked. The authors also acknowledged the need to validate the findings of this study in larger and more diverse cohorts.

DISCLOSURES:

This work was supported by the National Key Research and Development Program of China, Shanghai Municipal Key Clinical Specialty, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A fiber supplement also found in beans and other foods may lead to weight loss and improved insulin sensitivity in people with excess body weight, partly due to changes in the gut microbiota.

METHODOLOGY:

• In animal studies, resistant starch (RS), a kind of dietary fiber, has shown a potential to reduce body fat along with other metabolic benefits, but human dietary studies of RS have been inconsistent, especially with a high-fat diet.
• Researchers conducted a crossover, randomized trial to study the effect of RS as a dietary supplement on 37 individuals with overweight or obesity (average age, 33.43 years; 15 women; body mass index > 24 or higher waist circumference).
• Participants were fed a similar background diet and either 40 g of RS (high-amylose maize) or an energy-matched placebo starch daily for 8 weeks and then switched between the two in a separate 8-week period.
• The primary outcome was body weight, and the secondary outcomes were visceral and subcutaneous fat mass, waist circumference, lipid profiles, insulin sensitivity, metabolome, and gut microbiome.
• RS’s impact on gut microbiota composition and function was assessed with metagenomics and metabolomics, and RS-modified gut microbiota’s effect on host body fat and glucose was confirmed by transferring from select average participants to mice.

TAKEAWAY:

• Participants showed a mean weight loss of 2.8 kg after consuming RS for 8 weeks (P < .001), but there was no significant change in body weight in those on placebo starch.
• RS improved insulin sensitivity in people to a greater extent than placebo starch (P = .025) and showed a greater reduction in fat mass, waist circumference, and other obesity-related outcomes.
• The abundance in the gut of the microbe Bifidobacterium adolescentis increased significantly following RS intervention, an increase that exhibited a strong correlation with decreased BMI, suggesting a role of RS in reducing obesity.
• The levels of pro-inflammatory cytokines, such as serum tumor necrosis factor-alpha and interleukin-1 beta, were significantly lower in participants who consumed RS than in those who had placebo starch.

IN PRACTICE:

“Our study provided an effective dietary recommendation using RS as a supplement (40 g/d with a balanced background diet containing 25%-30% fat), which may help to achieve significant weight loss,” the authors wrote.

SOURCE:

This study was led and corresponded by Huating Li, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, and University of Hong Kong, Pok Fu Lam, and published online in Nature Metabolism.

LIMITATIONS:

This study was limited by the small sample size and stringent inclusion criteria for participants. The use of database-driven and taxane-based methodology might have led to difficult-to-classify sequences being discarded and strain-level functional diversity being overlooked. The authors also acknowledged the need to validate the findings of this study in larger and more diverse cohorts.

DISCLOSURES:

This work was supported by the National Key Research and Development Program of China, Shanghai Municipal Key Clinical Specialty, National Natural Science Foundation of China, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Mothers on vegan diets during pregnancy may give birth to infants with lower mean birth weights than those of omnivorous mothers and may also have a greater risk of preeclampsia, a prospective study of Danish pregnant women suggests.

According to researchers led by Signe Hedegaard, MD, of the department of obstetrics and Gynecology at Rigshospitalet, Juliane Marie Center, University of Copenhagen, low protein intake may lie behind the observed association with birth weight. The report was published in Acta Obstetricia et Gynecologica Scandinavica.

While vegan-identifying mothers were very few in number, the authors conceded, their babies were more likely to weigh less on average than those of omnivorous mothers — 3441 g vs 3601 g — despite a mean gestation 5 days longer.

Prevalence rates of low birth weight (< 2500 g) in the two groups were 11.1% and 2.5%, respectively, and the prevalence of preeclampsia was 11.1% vs 2.6%. The mean birth weight of infants in the maternal vegan group was about 240 g lower than infants born to omnivorous mothers.

“The lower birth weight of around 240 g among vegans compared with omnivorous mothers in our study strengthens our observation that vegans may be at higher risk of giving birth to low-birth-weight infants. The observed effect size on birth weight is comparable to what is observed among daily smokers relative to nonsmokers in this cohort,“ Dr. Hedegaard and colleagues wrote. “Furthermore, the on-average 5-day longer gestation observed among vegans in our study would be indicative of reduced fetal growth rate rather than lower birth weight due to shorter gestation.”

These findings emerged from data on 66,738 pregnancies in the Danish National Birth Cohort, 1996-2002. A food frequency questionnaire characterized pregnant subjects as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans, or omnivores, based on their self-reporting in gestational week 30.

A total of 98.7% (n = 65,872) of participants were defined as omnivorous, while 1.0% (n = 666), 0.3% (n = 183), and 0.03% (n = 18) identified as fish/poultry vegetarians, lacto/ovo-vegetarians, or vegans, respectively.

Those following plant-based diets of all types were slightly older, more often parous, and less likely to smoke. This plant dietary group also had a somewhat lower prevalence of overweight and obesity (prepregnancy body mass index > 25 [kg/m^2]) and a higher prevalence of underweight (prepregnancy BMI < 18.5).

Total energy intake was modestly lower from plant-based diets, for a mean difference of 0.3-0.7 MJ (72-167 kcal) per day.

As for total protein intake, this was substantially lower for lacto/ovo-vegetarians and vegans: 13.3% and 10.4% of energy, respectively, compared with 15.4% in omnivores.

Dietary intake of micronutrients was also considerably lower among vegans, but after factoring in intake from dietary supplements, no major differences emerged.

Mean birth weight, birth length, length of gestation, and rate of low birth weight (< 2500 g) were similar among omnivorous, fish/poultry-, and lacto/ovo-vegetarians. The prevalence of gestational diabetes, preeclampsia, and cesarean section was similar across groups, but the prevalence of anemia was higher among fish/poultry- and lacto/ovo-vegetarians than omnivorous participants.

As for preeclampsia, previous research in larger numbers of vegans found no indication of hypertensive disorders during pregnancy. Some studies, however, have suggested a link between preeclampsia and low intake of protein, calcium, or vitamin D, but the evidence is inconclusive, and the mechanism is unclear.

The observed associations, however, do not translate to causality, the authors cautioned. “Future studies should put more emphasis on characterizing the diet among those adhering to vegan diets and other forms of plant-based diets during pregnancy,” they wrote. “That would allow for stronger assumptions on possible causality between any association observed with birth or pregnancy outcomes in such studies and strengthen the basis for dietary recommendations.”

This study was funded by the Danish Council for Independent Research. The Danish National Birth Cohort Study is supported by the March of Dimes Birth Defects Foundation, the Danish Heart Association, Danish Medical Research Council, Sygekassernes Helsefond, the Innovation Fund Denmark, and the Danish National Research Foundation. The authors had no conflicts of interest to declare.

Mothers on vegan diets during pregnancy may give birth to infants with lower mean birth weights than those of omnivorous mothers and may also have a greater risk of preeclampsia, a prospective study of Danish pregnant women suggests.

According to researchers led by Signe Hedegaard, MD, of the department of obstetrics and Gynecology at Rigshospitalet, Juliane Marie Center, University of Copenhagen, low protein intake may lie behind the observed association with birth weight. The report was published in Acta Obstetricia et Gynecologica Scandinavica.

While vegan-identifying mothers were very few in number, the authors conceded, their babies were more likely to weigh less on average than those of omnivorous mothers — 3441 g vs 3601 g — despite a mean gestation 5 days longer.

Prevalence rates of low birth weight (< 2500 g) in the two groups were 11.1% and 2.5%, respectively, and the prevalence of preeclampsia was 11.1% vs 2.6%. The mean birth weight of infants in the maternal vegan group was about 240 g lower than infants born to omnivorous mothers.

“The lower birth weight of around 240 g among vegans compared with omnivorous mothers in our study strengthens our observation that vegans may be at higher risk of giving birth to low-birth-weight infants. The observed effect size on birth weight is comparable to what is observed among daily smokers relative to nonsmokers in this cohort,“ Dr. Hedegaard and colleagues wrote. “Furthermore, the on-average 5-day longer gestation observed among vegans in our study would be indicative of reduced fetal growth rate rather than lower birth weight due to shorter gestation.”

These findings emerged from data on 66,738 pregnancies in the Danish National Birth Cohort, 1996-2002. A food frequency questionnaire characterized pregnant subjects as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans, or omnivores, based on their self-reporting in gestational week 30.

A total of 98.7% (n = 65,872) of participants were defined as omnivorous, while 1.0% (n = 666), 0.3% (n = 183), and 0.03% (n = 18) identified as fish/poultry vegetarians, lacto/ovo-vegetarians, or vegans, respectively.

Those following plant-based diets of all types were slightly older, more often parous, and less likely to smoke. This plant dietary group also had a somewhat lower prevalence of overweight and obesity (prepregnancy body mass index > 25 [kg/m^2]) and a higher prevalence of underweight (prepregnancy BMI < 18.5).

Total energy intake was modestly lower from plant-based diets, for a mean difference of 0.3-0.7 MJ (72-167 kcal) per day.

As for total protein intake, this was substantially lower for lacto/ovo-vegetarians and vegans: 13.3% and 10.4% of energy, respectively, compared with 15.4% in omnivores.

Dietary intake of micronutrients was also considerably lower among vegans, but after factoring in intake from dietary supplements, no major differences emerged.

Mean birth weight, birth length, length of gestation, and rate of low birth weight (< 2500 g) were similar among omnivorous, fish/poultry-, and lacto/ovo-vegetarians. The prevalence of gestational diabetes, preeclampsia, and cesarean section was similar across groups, but the prevalence of anemia was higher among fish/poultry- and lacto/ovo-vegetarians than omnivorous participants.

As for preeclampsia, previous research in larger numbers of vegans found no indication of hypertensive disorders during pregnancy. Some studies, however, have suggested a link between preeclampsia and low intake of protein, calcium, or vitamin D, but the evidence is inconclusive, and the mechanism is unclear.

The observed associations, however, do not translate to causality, the authors cautioned. “Future studies should put more emphasis on characterizing the diet among those adhering to vegan diets and other forms of plant-based diets during pregnancy,” they wrote. “That would allow for stronger assumptions on possible causality between any association observed with birth or pregnancy outcomes in such studies and strengthen the basis for dietary recommendations.”

This study was funded by the Danish Council for Independent Research. The Danish National Birth Cohort Study is supported by the March of Dimes Birth Defects Foundation, the Danish Heart Association, Danish Medical Research Council, Sygekassernes Helsefond, the Innovation Fund Denmark, and the Danish National Research Foundation. The authors had no conflicts of interest to declare.

Mothers on vegan diets during pregnancy may give birth to infants with lower mean birth weights than those of omnivorous mothers and may also have a greater risk of preeclampsia, a prospective study of Danish pregnant women suggests.

According to researchers led by Signe Hedegaard, MD, of the department of obstetrics and Gynecology at Rigshospitalet, Juliane Marie Center, University of Copenhagen, low protein intake may lie behind the observed association with birth weight. The report was published in Acta Obstetricia et Gynecologica Scandinavica.

While vegan-identifying mothers were very few in number, the authors conceded, their babies were more likely to weigh less on average than those of omnivorous mothers — 3441 g vs 3601 g — despite a mean gestation 5 days longer.

Prevalence rates of low birth weight (< 2500 g) in the two groups were 11.1% and 2.5%, respectively, and the prevalence of preeclampsia was 11.1% vs 2.6%. The mean birth weight of infants in the maternal vegan group was about 240 g lower than infants born to omnivorous mothers.

“The lower birth weight of around 240 g among vegans compared with omnivorous mothers in our study strengthens our observation that vegans may be at higher risk of giving birth to low-birth-weight infants. The observed effect size on birth weight is comparable to what is observed among daily smokers relative to nonsmokers in this cohort,“ Dr. Hedegaard and colleagues wrote. “Furthermore, the on-average 5-day longer gestation observed among vegans in our study would be indicative of reduced fetal growth rate rather than lower birth weight due to shorter gestation.”

These findings emerged from data on 66,738 pregnancies in the Danish National Birth Cohort, 1996-2002. A food frequency questionnaire characterized pregnant subjects as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans, or omnivores, based on their self-reporting in gestational week 30.

A total of 98.7% (n = 65,872) of participants were defined as omnivorous, while 1.0% (n = 666), 0.3% (n = 183), and 0.03% (n = 18) identified as fish/poultry vegetarians, lacto/ovo-vegetarians, or vegans, respectively.

Those following plant-based diets of all types were slightly older, more often parous, and less likely to smoke. This plant dietary group also had a somewhat lower prevalence of overweight and obesity (prepregnancy body mass index > 25 [kg/m^2]) and a higher prevalence of underweight (prepregnancy BMI < 18.5).

Total energy intake was modestly lower from plant-based diets, for a mean difference of 0.3-0.7 MJ (72-167 kcal) per day.

As for total protein intake, this was substantially lower for lacto/ovo-vegetarians and vegans: 13.3% and 10.4% of energy, respectively, compared with 15.4% in omnivores.

Dietary intake of micronutrients was also considerably lower among vegans, but after factoring in intake from dietary supplements, no major differences emerged.

Mean birth weight, birth length, length of gestation, and rate of low birth weight (< 2500 g) were similar among omnivorous, fish/poultry-, and lacto/ovo-vegetarians. The prevalence of gestational diabetes, preeclampsia, and cesarean section was similar across groups, but the prevalence of anemia was higher among fish/poultry- and lacto/ovo-vegetarians than omnivorous participants.

As for preeclampsia, previous research in larger numbers of vegans found no indication of hypertensive disorders during pregnancy. Some studies, however, have suggested a link between preeclampsia and low intake of protein, calcium, or vitamin D, but the evidence is inconclusive, and the mechanism is unclear.

The observed associations, however, do not translate to causality, the authors cautioned. “Future studies should put more emphasis on characterizing the diet among those adhering to vegan diets and other forms of plant-based diets during pregnancy,” they wrote. “That would allow for stronger assumptions on possible causality between any association observed with birth or pregnancy outcomes in such studies and strengthen the basis for dietary recommendations.”

This study was funded by the Danish Council for Independent Research. The Danish National Birth Cohort Study is supported by the March of Dimes Birth Defects Foundation, the Danish Heart Association, Danish Medical Research Council, Sygekassernes Helsefond, the Innovation Fund Denmark, and the Danish National Research Foundation. The authors had no conflicts of interest to declare.

TOPLINE:

New data link smoking and heavy drinking with an increased risk for diverticulitis, with the greatest risk seen in adults who smoke and consume two or more drinks daily.

METHODOLOGY:

• Researchers studied 84,232 women in the Nurses’ Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. 
• In 2015 and 2017, participants were asked via questionnaire whether they had been diagnosed with diverticulitis requiring antibiotic therapy or hospitalization. Diverticulitis was defined as a computed tomography scan or pathology report of diverticulitis or a provider diagnosis with a clinical presentation consistent with diverticulitis. 
• Smoking was assessed every 2 years and alcohol consumption every 4 years using standard questionnaires. 
• Consistent with prior studies on risk factors for diverticulitis, multivariable models adjusted for age, menopausal hormone status and hormone use, body mass index, physical activity, aspirin/nonsteroidal anti-inflammatory drug use, intake of fiber and red/processed meat, and other factors were used. 

TAKEAWAY:

• During more than 1 million person-years of follow-up, 3018 incident cases of diverticulitis were identified. 
• Both current and past smoking were associated with increased risk for diverticulitis (hazard ratio [HR], 1.2) compared with never smoking, although no dose-response relationship was evident. In an analysis restricted to participants who had surgery for diverticulitis, the magnitude of the association was strengthened (HR, 1.48 for current smokers and 1.46 for past smokers vs never smokers). 
• Consumption of ≥ 30 g/d of alcohol (2+ drinks/day) was associated with an increased risk for incident diverticulitis (HR, 1.26) compared with not drinking. 
• A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥ 30 g/d of alcohol were at the highest risk for diverticulitis (multivariate HR, 1.53) compared with individuals who never smoked and reported no alcohol use. 

IN PRACTICE:

“As there are currently no medical means to prevent diverticulitis other than dietary and lifestyle interventions, counseling patients about the avoidance of smoking and alcohol may help lower the risk for developing diverticulitis,” the authors concluded.

SOURCE:

The study, with first author Sara Gunby, MD, University of Washington School of Medicine, Seattle, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Diverticulitis diagnoses were self-reported, although a review of a subset of medical records confirmed the diagnosis in more than 90% of cases establishing the validity of self-report in this population. The study was limited to female nurses, so it is possible the findings may not be generalizable to men or other populations. Residual confounding may have impacted the results.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

New data link smoking and heavy drinking with an increased risk for diverticulitis, with the greatest risk seen in adults who smoke and consume two or more drinks daily.

METHODOLOGY:

• Researchers studied 84,232 women in the Nurses’ Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. 
• In 2015 and 2017, participants were asked via questionnaire whether they had been diagnosed with diverticulitis requiring antibiotic therapy or hospitalization. Diverticulitis was defined as a computed tomography scan or pathology report of diverticulitis or a provider diagnosis with a clinical presentation consistent with diverticulitis. 
• Smoking was assessed every 2 years and alcohol consumption every 4 years using standard questionnaires. 
• Consistent with prior studies on risk factors for diverticulitis, multivariable models adjusted for age, menopausal hormone status and hormone use, body mass index, physical activity, aspirin/nonsteroidal anti-inflammatory drug use, intake of fiber and red/processed meat, and other factors were used. 

TAKEAWAY:

• During more than 1 million person-years of follow-up, 3018 incident cases of diverticulitis were identified. 
• Both current and past smoking were associated with increased risk for diverticulitis (hazard ratio [HR], 1.2) compared with never smoking, although no dose-response relationship was evident. In an analysis restricted to participants who had surgery for diverticulitis, the magnitude of the association was strengthened (HR, 1.48 for current smokers and 1.46 for past smokers vs never smokers). 
• Consumption of ≥ 30 g/d of alcohol (2+ drinks/day) was associated with an increased risk for incident diverticulitis (HR, 1.26) compared with not drinking. 
• A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥ 30 g/d of alcohol were at the highest risk for diverticulitis (multivariate HR, 1.53) compared with individuals who never smoked and reported no alcohol use. 

IN PRACTICE:

“As there are currently no medical means to prevent diverticulitis other than dietary and lifestyle interventions, counseling patients about the avoidance of smoking and alcohol may help lower the risk for developing diverticulitis,” the authors concluded.

SOURCE:

The study, with first author Sara Gunby, MD, University of Washington School of Medicine, Seattle, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Diverticulitis diagnoses were self-reported, although a review of a subset of medical records confirmed the diagnosis in more than 90% of cases establishing the validity of self-report in this population. The study was limited to female nurses, so it is possible the findings may not be generalizable to men or other populations. Residual confounding may have impacted the results.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

New data link smoking and heavy drinking with an increased risk for diverticulitis, with the greatest risk seen in adults who smoke and consume two or more drinks daily.

METHODOLOGY:

• Researchers studied 84,232 women in the Nurses’ Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. 
• In 2015 and 2017, participants were asked via questionnaire whether they had been diagnosed with diverticulitis requiring antibiotic therapy or hospitalization. Diverticulitis was defined as a computed tomography scan or pathology report of diverticulitis or a provider diagnosis with a clinical presentation consistent with diverticulitis. 
• Smoking was assessed every 2 years and alcohol consumption every 4 years using standard questionnaires. 
• Consistent with prior studies on risk factors for diverticulitis, multivariable models adjusted for age, menopausal hormone status and hormone use, body mass index, physical activity, aspirin/nonsteroidal anti-inflammatory drug use, intake of fiber and red/processed meat, and other factors were used. 

TAKEAWAY:

• During more than 1 million person-years of follow-up, 3018 incident cases of diverticulitis were identified. 
• Both current and past smoking were associated with increased risk for diverticulitis (hazard ratio [HR], 1.2) compared with never smoking, although no dose-response relationship was evident. In an analysis restricted to participants who had surgery for diverticulitis, the magnitude of the association was strengthened (HR, 1.48 for current smokers and 1.46 for past smokers vs never smokers). 
• Consumption of ≥ 30 g/d of alcohol (2+ drinks/day) was associated with an increased risk for incident diverticulitis (HR, 1.26) compared with not drinking. 
• A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥ 30 g/d of alcohol were at the highest risk for diverticulitis (multivariate HR, 1.53) compared with individuals who never smoked and reported no alcohol use. 

IN PRACTICE:

“As there are currently no medical means to prevent diverticulitis other than dietary and lifestyle interventions, counseling patients about the avoidance of smoking and alcohol may help lower the risk for developing diverticulitis,” the authors concluded.

SOURCE:

The study, with first author Sara Gunby, MD, University of Washington School of Medicine, Seattle, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Diverticulitis diagnoses were self-reported, although a review of a subset of medical records confirmed the diagnosis in more than 90% of cases establishing the validity of self-report in this population. The study was limited to female nurses, so it is possible the findings may not be generalizable to men or other populations. Residual confounding may have impacted the results.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.