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Study: Healthy Plant-Based Diets Do Not Raise Hip Fracture Risk
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.
“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.
“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.
“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.
FROM JAMA NETWORK OPEN
Real-World Dupilumab Wins in Treating Refractory EoE
Most patients achieved histologic, endoscopic, and symptom improvement with a median of 6 months’ treatment with the interleukin 4 and 13 blocker, and esophageal stricture diameter improved as well, according to a single-center retrospective study in Clinical Gastroenterology and Hepatology.
“Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials,” concluded gastroenterologists Christopher J. Lee, MD (lead author), and Evan S. Dellon, MD, MPH, AGAF, of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine in Chapel Hill.
These real-world findings aligned with data from the group’s phase 3 clinical trial.
In addition, several case reports or series have highlighted the real-world efficacy of dupilumab, with a particular focus on pediatric patients and those with other atopic diseases.
“Despite nonresponse to prior treatments, these patients can likely expect to see results similar to what was seen in the clinical trial,” Dr. Dellon said in an interview. “However, it would be good to have similar confirmatory data from other centers, and I’m sure those data will be forthcoming as more EoE patients are treated with dupilumab.”
The placement of dupilumab in the EoE treatment algorithm is still actively being investigated. “While the phase 3 study led to [Food and Drug Administration] approval, it had strict inclusion and exclusion criteria, and some populations were ineligible,” he added. “In particular, the very severe EoE patients who either had a very narrow esophagus where the scope wouldn’t pass, or who had severe strictures and symptoms requiring esophageal dilation and who couldn’t go 6 to 12 months without dilation, couldn’t be enrolled. So the efficacy of dupilumab in this more severe group was not known.”
The group hypothesized that dupilumab would be effective in this population but did not know if the efficacy would be similar to that in the clinical trial. “The overall response rates, which were very similar to what were seen in the phase 3 trial, were surprising,“ Dr. Dellon said.”The other surprising finding was the increase in esophageal caliber, as measured by the size achieved with esophageal dilation.”
The study
The investigators identified 46 patients treated with dupilumab for refractory fibrostenotic EoE at the university’s medical center. All had failed or lost response to one or more standard therapies such as proton pump inhibitors, topical glucocorticosteroids, and a food elimination diet.
Previous treatments also included systemic steroids, cromolyn, ketotifen, montelukast, and 6-mercaptopurine, all with minimal response. Some 85% of patients had undergone an average of 9.0+ 7.0 pre-dupilumab dilations.
The biologic was initially prescribed off-label before FDA approval. Patients received it at a dose of 300 mg subcutaneously either fortnightly (n = 16) or weekly (n = 30), depending on insurance approval and timing of prescription. Length of treatment varied based on the time from prescription to first post-treatment evaluative endoscopy.
Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the pre-dupilumab esophagogastroduodenoscopies.
Among the specific findings:
- Peak eosinophil counts significantly decreased.
- Post-dupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field, and 6 or fewer eosinophils per high-power field, respectively.
- The Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all).
- Pre-dilation esophageal diameter increased from 13.9 to 16.0 mm (P < .001), although the proportion of strictures was stable.
- Global symptom improvement was reported in 91% of patients (P < .001).
Commenting on the study but not involved in it, David A. Katzka, MD, professor of medicine at Columbia University in New York City, said the findings would be of immediate use to practicing gastroenterologists.
“It’s necessary to do clinical trials, but real-world data make the clinician feel more comfortable in prescribing. Interestingly, I am seeing dupilumab being recommended not just for refractory disease but also as first-line therapy,” he said.
Dr. Dellon noted that the incidence and prevalence of EoE are rising rapidly in the US and around the world. “This increase is outpacing growing recognition of the disease,” he said. “Most likely, environmental factors are driving this change.” He called for studies to determine the long-term efficacy of dupilumab for this severe subgroup — and the potential benefit of moving dupilumab earlier into the treatment algorithm.
The latter is a controversial question, noted Dr. Katzka. “For patients with other indications such as asthma or eczema, dupilumab is the ideal medication,” he said. And it can be a first-line therapy if there are contraindications to alternatives or if compliance will be better with a once-weekly injection as opposed to a twice-daily medication or a food elimination diet. But overall, our more established therapies should be considered first.”
Dr. Katzka emphasized the need to further define EoE phenotypes in order to personalize therapy. “There’s likely a group of patients who should go straight to dupilumab, perhaps those marked by factors such as severity, progression, young age, or other atopic disorders. But we have yet to definitively identify this group.”
The authors reported no specific funding for this analysis. Dr. Dellon reported research funding and/or consulting fees from multiple pharmaceutical companies, including Regeneron/Sanofi, the developers of dupilumab. Dr. Lee had no competing interests to disclose. Dr. Katzka reported consulting for Medtronic, and is an associate editor for GI & Hepatology News.
Most patients achieved histologic, endoscopic, and symptom improvement with a median of 6 months’ treatment with the interleukin 4 and 13 blocker, and esophageal stricture diameter improved as well, according to a single-center retrospective study in Clinical Gastroenterology and Hepatology.
“Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials,” concluded gastroenterologists Christopher J. Lee, MD (lead author), and Evan S. Dellon, MD, MPH, AGAF, of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine in Chapel Hill.
These real-world findings aligned with data from the group’s phase 3 clinical trial.
In addition, several case reports or series have highlighted the real-world efficacy of dupilumab, with a particular focus on pediatric patients and those with other atopic diseases.
“Despite nonresponse to prior treatments, these patients can likely expect to see results similar to what was seen in the clinical trial,” Dr. Dellon said in an interview. “However, it would be good to have similar confirmatory data from other centers, and I’m sure those data will be forthcoming as more EoE patients are treated with dupilumab.”
The placement of dupilumab in the EoE treatment algorithm is still actively being investigated. “While the phase 3 study led to [Food and Drug Administration] approval, it had strict inclusion and exclusion criteria, and some populations were ineligible,” he added. “In particular, the very severe EoE patients who either had a very narrow esophagus where the scope wouldn’t pass, or who had severe strictures and symptoms requiring esophageal dilation and who couldn’t go 6 to 12 months without dilation, couldn’t be enrolled. So the efficacy of dupilumab in this more severe group was not known.”
The group hypothesized that dupilumab would be effective in this population but did not know if the efficacy would be similar to that in the clinical trial. “The overall response rates, which were very similar to what were seen in the phase 3 trial, were surprising,“ Dr. Dellon said.”The other surprising finding was the increase in esophageal caliber, as measured by the size achieved with esophageal dilation.”
The study
The investigators identified 46 patients treated with dupilumab for refractory fibrostenotic EoE at the university’s medical center. All had failed or lost response to one or more standard therapies such as proton pump inhibitors, topical glucocorticosteroids, and a food elimination diet.
Previous treatments also included systemic steroids, cromolyn, ketotifen, montelukast, and 6-mercaptopurine, all with minimal response. Some 85% of patients had undergone an average of 9.0+ 7.0 pre-dupilumab dilations.
The biologic was initially prescribed off-label before FDA approval. Patients received it at a dose of 300 mg subcutaneously either fortnightly (n = 16) or weekly (n = 30), depending on insurance approval and timing of prescription. Length of treatment varied based on the time from prescription to first post-treatment evaluative endoscopy.
Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the pre-dupilumab esophagogastroduodenoscopies.
Among the specific findings:
- Peak eosinophil counts significantly decreased.
- Post-dupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field, and 6 or fewer eosinophils per high-power field, respectively.
- The Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all).
- Pre-dilation esophageal diameter increased from 13.9 to 16.0 mm (P < .001), although the proportion of strictures was stable.
- Global symptom improvement was reported in 91% of patients (P < .001).
Commenting on the study but not involved in it, David A. Katzka, MD, professor of medicine at Columbia University in New York City, said the findings would be of immediate use to practicing gastroenterologists.
“It’s necessary to do clinical trials, but real-world data make the clinician feel more comfortable in prescribing. Interestingly, I am seeing dupilumab being recommended not just for refractory disease but also as first-line therapy,” he said.
Dr. Dellon noted that the incidence and prevalence of EoE are rising rapidly in the US and around the world. “This increase is outpacing growing recognition of the disease,” he said. “Most likely, environmental factors are driving this change.” He called for studies to determine the long-term efficacy of dupilumab for this severe subgroup — and the potential benefit of moving dupilumab earlier into the treatment algorithm.
The latter is a controversial question, noted Dr. Katzka. “For patients with other indications such as asthma or eczema, dupilumab is the ideal medication,” he said. And it can be a first-line therapy if there are contraindications to alternatives or if compliance will be better with a once-weekly injection as opposed to a twice-daily medication or a food elimination diet. But overall, our more established therapies should be considered first.”
Dr. Katzka emphasized the need to further define EoE phenotypes in order to personalize therapy. “There’s likely a group of patients who should go straight to dupilumab, perhaps those marked by factors such as severity, progression, young age, or other atopic disorders. But we have yet to definitively identify this group.”
The authors reported no specific funding for this analysis. Dr. Dellon reported research funding and/or consulting fees from multiple pharmaceutical companies, including Regeneron/Sanofi, the developers of dupilumab. Dr. Lee had no competing interests to disclose. Dr. Katzka reported consulting for Medtronic, and is an associate editor for GI & Hepatology News.
Most patients achieved histologic, endoscopic, and symptom improvement with a median of 6 months’ treatment with the interleukin 4 and 13 blocker, and esophageal stricture diameter improved as well, according to a single-center retrospective study in Clinical Gastroenterology and Hepatology.
“Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials,” concluded gastroenterologists Christopher J. Lee, MD (lead author), and Evan S. Dellon, MD, MPH, AGAF, of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine in Chapel Hill.
These real-world findings aligned with data from the group’s phase 3 clinical trial.
In addition, several case reports or series have highlighted the real-world efficacy of dupilumab, with a particular focus on pediatric patients and those with other atopic diseases.
“Despite nonresponse to prior treatments, these patients can likely expect to see results similar to what was seen in the clinical trial,” Dr. Dellon said in an interview. “However, it would be good to have similar confirmatory data from other centers, and I’m sure those data will be forthcoming as more EoE patients are treated with dupilumab.”
The placement of dupilumab in the EoE treatment algorithm is still actively being investigated. “While the phase 3 study led to [Food and Drug Administration] approval, it had strict inclusion and exclusion criteria, and some populations were ineligible,” he added. “In particular, the very severe EoE patients who either had a very narrow esophagus where the scope wouldn’t pass, or who had severe strictures and symptoms requiring esophageal dilation and who couldn’t go 6 to 12 months without dilation, couldn’t be enrolled. So the efficacy of dupilumab in this more severe group was not known.”
The group hypothesized that dupilumab would be effective in this population but did not know if the efficacy would be similar to that in the clinical trial. “The overall response rates, which were very similar to what were seen in the phase 3 trial, were surprising,“ Dr. Dellon said.”The other surprising finding was the increase in esophageal caliber, as measured by the size achieved with esophageal dilation.”
The study
The investigators identified 46 patients treated with dupilumab for refractory fibrostenotic EoE at the university’s medical center. All had failed or lost response to one or more standard therapies such as proton pump inhibitors, topical glucocorticosteroids, and a food elimination diet.
Previous treatments also included systemic steroids, cromolyn, ketotifen, montelukast, and 6-mercaptopurine, all with minimal response. Some 85% of patients had undergone an average of 9.0+ 7.0 pre-dupilumab dilations.
The biologic was initially prescribed off-label before FDA approval. Patients received it at a dose of 300 mg subcutaneously either fortnightly (n = 16) or weekly (n = 30), depending on insurance approval and timing of prescription. Length of treatment varied based on the time from prescription to first post-treatment evaluative endoscopy.
Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the pre-dupilumab esophagogastroduodenoscopies.
Among the specific findings:
- Peak eosinophil counts significantly decreased.
- Post-dupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field, and 6 or fewer eosinophils per high-power field, respectively.
- The Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all).
- Pre-dilation esophageal diameter increased from 13.9 to 16.0 mm (P < .001), although the proportion of strictures was stable.
- Global symptom improvement was reported in 91% of patients (P < .001).
Commenting on the study but not involved in it, David A. Katzka, MD, professor of medicine at Columbia University in New York City, said the findings would be of immediate use to practicing gastroenterologists.
“It’s necessary to do clinical trials, but real-world data make the clinician feel more comfortable in prescribing. Interestingly, I am seeing dupilumab being recommended not just for refractory disease but also as first-line therapy,” he said.
Dr. Dellon noted that the incidence and prevalence of EoE are rising rapidly in the US and around the world. “This increase is outpacing growing recognition of the disease,” he said. “Most likely, environmental factors are driving this change.” He called for studies to determine the long-term efficacy of dupilumab for this severe subgroup — and the potential benefit of moving dupilumab earlier into the treatment algorithm.
The latter is a controversial question, noted Dr. Katzka. “For patients with other indications such as asthma or eczema, dupilumab is the ideal medication,” he said. And it can be a first-line therapy if there are contraindications to alternatives or if compliance will be better with a once-weekly injection as opposed to a twice-daily medication or a food elimination diet. But overall, our more established therapies should be considered first.”
Dr. Katzka emphasized the need to further define EoE phenotypes in order to personalize therapy. “There’s likely a group of patients who should go straight to dupilumab, perhaps those marked by factors such as severity, progression, young age, or other atopic disorders. But we have yet to definitively identify this group.”
The authors reported no specific funding for this analysis. Dr. Dellon reported research funding and/or consulting fees from multiple pharmaceutical companies, including Regeneron/Sanofi, the developers of dupilumab. Dr. Lee had no competing interests to disclose. Dr. Katzka reported consulting for Medtronic, and is an associate editor for GI & Hepatology News.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AHA: Urgent Need To Reduce Maternal Postpartum CVD Risk
Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.
The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.
“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.
“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.
APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.
Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.
The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.
An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.
Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.
Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.
Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”
Dr. Cameron also noted that new research suggests the mother’s cardiovascular health during pregnancy can affect the child’s health through adolescence. “There’s a potential intergenerational effect and there may even be some programming and changes to the offspring in utero related to maternal lifestyle factors.”
While the postpartum period would seem like an opportune time to piggyback postpartum visits with infant wellness checkups, “the fact is that, in the U.S., many mothers are lost to care after delivery,” Dr. Lewey said. “But it’s essential to ensure transition to postpartum care.”
According to Dr. Cameron, physicians should be aware of the risk factor data and educate their pregnant and postpartum patients about reducing risk factors. “As I like to say, ‘If you’re going to take care of others, you need to take care of yourself first.’ ” While this statement may be a good starting point, future trials are needed to improve screening for subclinical CVD in individuals with APOs before symptom onset, the statement authors wrote.
This scientific statement was prepared on behalf of the American Heart Association. Dr. Lewey and several coauthors reported research funding from various agencies within the National Institutes of Health. Dr. Brown reported research funding from a cy-près court settlement with Wyeth. Dr. Cameron had no competing interests relevant to her comments.
Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.
The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.
“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.
“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.
APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.
Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.
The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.
An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.
Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.
Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.
Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”
Dr. Cameron also noted that new research suggests the mother’s cardiovascular health during pregnancy can affect the child’s health through adolescence. “There’s a potential intergenerational effect and there may even be some programming and changes to the offspring in utero related to maternal lifestyle factors.”
While the postpartum period would seem like an opportune time to piggyback postpartum visits with infant wellness checkups, “the fact is that, in the U.S., many mothers are lost to care after delivery,” Dr. Lewey said. “But it’s essential to ensure transition to postpartum care.”
According to Dr. Cameron, physicians should be aware of the risk factor data and educate their pregnant and postpartum patients about reducing risk factors. “As I like to say, ‘If you’re going to take care of others, you need to take care of yourself first.’ ” While this statement may be a good starting point, future trials are needed to improve screening for subclinical CVD in individuals with APOs before symptom onset, the statement authors wrote.
This scientific statement was prepared on behalf of the American Heart Association. Dr. Lewey and several coauthors reported research funding from various agencies within the National Institutes of Health. Dr. Brown reported research funding from a cy-près court settlement with Wyeth. Dr. Cameron had no competing interests relevant to her comments.
Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.
The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.
“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.
“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.
APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.
Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.
The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.
An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.
Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.
Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.
Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”
Dr. Cameron also noted that new research suggests the mother’s cardiovascular health during pregnancy can affect the child’s health through adolescence. “There’s a potential intergenerational effect and there may even be some programming and changes to the offspring in utero related to maternal lifestyle factors.”
While the postpartum period would seem like an opportune time to piggyback postpartum visits with infant wellness checkups, “the fact is that, in the U.S., many mothers are lost to care after delivery,” Dr. Lewey said. “But it’s essential to ensure transition to postpartum care.”
According to Dr. Cameron, physicians should be aware of the risk factor data and educate their pregnant and postpartum patients about reducing risk factors. “As I like to say, ‘If you’re going to take care of others, you need to take care of yourself first.’ ” While this statement may be a good starting point, future trials are needed to improve screening for subclinical CVD in individuals with APOs before symptom onset, the statement authors wrote.
This scientific statement was prepared on behalf of the American Heart Association. Dr. Lewey and several coauthors reported research funding from various agencies within the National Institutes of Health. Dr. Brown reported research funding from a cy-près court settlement with Wyeth. Dr. Cameron had no competing interests relevant to her comments.
FROM CIRCULATION
Telephone Best for Switching Patients to New Colonoscopy Intervals
In an article published in Clinical Gastroenterology and Hepatology, a group led by Jeffrey K. Lee, MD, MPH, a gastroenterologist at Kaiser Permanente Medical Center in San Francisco, reported the following 60-day response rates for the three contact methods in potentially transitioning more than 600 post-polypectomy patients to the new interval:
- Telephone: 64.5%
- Secure messaging: 51.7%
- Mailed letter: 31.3%
Compared with letter outreach, overall rate differences were significant for telephone (18.1%) and secure message outreach (13.1%).
Such interventions are widely used, the authors noted , but have not been compared for efficacy terms of communicating updated colonoscopy intervals.
The trial’s aim was to inform low-risk patients of the recommended interval update from 5 years — used since the 1990s — to 7-10 years. Given a choice, more patients opted to transition to the 10-year surveillance interval in the telephone (37%) and secure messaging arms (32.%) compared with mailed-letter arm (18.9%).
In addition to telephone and secure messaging outreach, factors positively associated with adoption of the 10-year interval were a positive fecal immunochemical test–based index colonoscopy and increasing age. Patients with these characteristics may be biased toward avoiding colonoscopy if not medically necessary, the authors conjectured.
Inversely associated factors included Asian or Pacific Islander race (odds ratio .58), Hispanic ethnicity (OR .40), and a higher Charlson comorbidity score of 2 vs 0 (OR .43).
Possible explanations for the race and ethnicity associations include gaps in culturally component care, lack of engagement with the English-based outreach approaches, and medical mistrust, the authors said.
“In this study, we gave all our patients an option to either extend their surveillance interval to current guideline recommendations or continue with their old interval, and some chose to do that,” Dr. Lee said in an interview. “Patients really appreciated having a choice and to be informed about the latest guideline changes.”
“A critical challenge to health systems is how to effectively de-implement outdated surveillance recommendations for low-risk patients who have a 5-year follow-up interval and potentially transition them to the recommended 7- to 10-year interval,” Dr. Lee and colleagues wrote.
More than 5 million surveillance colonoscopies are performed annually in US patients with a history of adenomas, the main precursor lesion for colorectal cancer, the authors noted.
With the recent guidelines issued in 2020 by the US Multi-Society Task Force on Colorectal Cancer lengthening the follow-up interval to 7-10 years , physicians are being advised to reevaluate low-risk patients previously scheduled with 5-year surveillance and provide an updated recommendation for follow-up.
Study Details
The three-arm pragmatic randomized trial was conducted in low-risk patients 54-70 years of age with one or two small (< 10 mm) tubular adenomas at baseline colonoscopy. Participants due for 5-year surveillance in 2022 were randomly assigned to one of three outreach arms: telephone (n = 200], secure messaging (n = 203), and mailed letter (n = 201). Stratified by age, sex, race, and ethnicity, participants could change their assigned interval to 10 years or continue with their previously scheduled 5-year interval.
As to economic considerations, the authors said that telephone may be the costliest form of outreach in terms of staffing resources. “We don’t know because we did not conduct a formal cost-effectiveness analysis,” Dr. Lee said. “However, we do know phone outreach requires a lot of personnel effort, which is why we also explored the less costly option of secure messaging/email.”
But based on the findings, telephone outreach would be a reasonable approach to update patients on post-polypectomy surveillance guideline changes if secure messaging or text messaging isn’t available, he added.
Downsides to Retroactive Changes?
Commenting on the study but not involved in it, Nabil M. Mansour, MD, an assistant professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, noted that unlike Kaiser Permanente, his center decided against an overall effort to switch patients colonoscopied before the release of the new guidelines over to the new interval.
“Several of our physicians may have chosen to recommend a 5-year interval specifically for a variety of reasons and we felt going back, and making a blanket change to everyone’s interval retrospectively might create confusion and frustration and might actually delay the colonoscopies of some patients for which their doctors had a very good, legitimate reason to recommend a 5-year interval,” he said in an interview.
Dr. Mansour added that no difficulties were encountered in getting patients to agree to a 10-year interval. In his view telephone communication or in-person clinic visits are likely the most effective ways but both are more labor-intensive than automated patient portal messages. “I do not think traditional snail mail is effective.” His clinic uses automatic EMR reminders.
Offering another perspective on the study, Aditya Sreenivasan, MD, a gastroenterologist at Northwell Health in New York City, said his center has not reached out to correct the old intervals. “When I see a patient who previously had a colonoscopy with another physician, I always follow the previous recommendation for when the next colonoscopy should be, regardless of whether or not it technically meets guideline recommendations,” he told this news organization. “I do this because I was not there during the procedure and am not aware of any circumstances that would require a shorter interval that may not be apparent from the report.”
While he agrees with the new guidelines, Dr. Sreenivasan is “not sure if retroactively changing intervals is beneficial to patients, as the presence of guidelines may subconsciously influence the behavior of the endoscopist at the time of the procedure. For example, if a patient has a technically challenging colonoscopy and the endoscopist is running late, the endoscopist may drop their guard once they find a polyp and miss 1-2 additional small polyps that they would have spent more time looking for if they knew their next one would be in 10 years instead of 5.”
As for notification method, despite the logistical downside of taking dedicated staff time to make telephone calls, Dr. Sreenivasan said, “I think having a conversation with the patient directly is a much better way to communicate this information as it allows the patient to ask and answer questions. Things like tone of voice can provide reassurance that one cannot get via email.” Looking to the future, the study authors acknowledged that combinations of initial and reminder outreach approaches — for example, a mailed letter followed by secure message or telephone call — could potentially yield higher response rates and/or adoption rates than they observed. And a longer follow-up period with additional reminders may have produced higher yields. Additional studies are needed to optimize outreach approaches and to understand patient barriers to adopting the new guideline recommendations in different healthcare settings.
The study was supported by a Delivery Science grant from the Kaiser Permanente Northern California.
The authors disclosed no conflicts of interest. Dr. Mansour and Dr. Sreenivasan disclosed no conflicts of interest relevant to their comments.
In an article published in Clinical Gastroenterology and Hepatology, a group led by Jeffrey K. Lee, MD, MPH, a gastroenterologist at Kaiser Permanente Medical Center in San Francisco, reported the following 60-day response rates for the three contact methods in potentially transitioning more than 600 post-polypectomy patients to the new interval:
- Telephone: 64.5%
- Secure messaging: 51.7%
- Mailed letter: 31.3%
Compared with letter outreach, overall rate differences were significant for telephone (18.1%) and secure message outreach (13.1%).
Such interventions are widely used, the authors noted , but have not been compared for efficacy terms of communicating updated colonoscopy intervals.
The trial’s aim was to inform low-risk patients of the recommended interval update from 5 years — used since the 1990s — to 7-10 years. Given a choice, more patients opted to transition to the 10-year surveillance interval in the telephone (37%) and secure messaging arms (32.%) compared with mailed-letter arm (18.9%).
In addition to telephone and secure messaging outreach, factors positively associated with adoption of the 10-year interval were a positive fecal immunochemical test–based index colonoscopy and increasing age. Patients with these characteristics may be biased toward avoiding colonoscopy if not medically necessary, the authors conjectured.
Inversely associated factors included Asian or Pacific Islander race (odds ratio .58), Hispanic ethnicity (OR .40), and a higher Charlson comorbidity score of 2 vs 0 (OR .43).
Possible explanations for the race and ethnicity associations include gaps in culturally component care, lack of engagement with the English-based outreach approaches, and medical mistrust, the authors said.
“In this study, we gave all our patients an option to either extend their surveillance interval to current guideline recommendations or continue with their old interval, and some chose to do that,” Dr. Lee said in an interview. “Patients really appreciated having a choice and to be informed about the latest guideline changes.”
“A critical challenge to health systems is how to effectively de-implement outdated surveillance recommendations for low-risk patients who have a 5-year follow-up interval and potentially transition them to the recommended 7- to 10-year interval,” Dr. Lee and colleagues wrote.
More than 5 million surveillance colonoscopies are performed annually in US patients with a history of adenomas, the main precursor lesion for colorectal cancer, the authors noted.
With the recent guidelines issued in 2020 by the US Multi-Society Task Force on Colorectal Cancer lengthening the follow-up interval to 7-10 years , physicians are being advised to reevaluate low-risk patients previously scheduled with 5-year surveillance and provide an updated recommendation for follow-up.
Study Details
The three-arm pragmatic randomized trial was conducted in low-risk patients 54-70 years of age with one or two small (< 10 mm) tubular adenomas at baseline colonoscopy. Participants due for 5-year surveillance in 2022 were randomly assigned to one of three outreach arms: telephone (n = 200], secure messaging (n = 203), and mailed letter (n = 201). Stratified by age, sex, race, and ethnicity, participants could change their assigned interval to 10 years or continue with their previously scheduled 5-year interval.
As to economic considerations, the authors said that telephone may be the costliest form of outreach in terms of staffing resources. “We don’t know because we did not conduct a formal cost-effectiveness analysis,” Dr. Lee said. “However, we do know phone outreach requires a lot of personnel effort, which is why we also explored the less costly option of secure messaging/email.”
But based on the findings, telephone outreach would be a reasonable approach to update patients on post-polypectomy surveillance guideline changes if secure messaging or text messaging isn’t available, he added.
Downsides to Retroactive Changes?
Commenting on the study but not involved in it, Nabil M. Mansour, MD, an assistant professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, noted that unlike Kaiser Permanente, his center decided against an overall effort to switch patients colonoscopied before the release of the new guidelines over to the new interval.
“Several of our physicians may have chosen to recommend a 5-year interval specifically for a variety of reasons and we felt going back, and making a blanket change to everyone’s interval retrospectively might create confusion and frustration and might actually delay the colonoscopies of some patients for which their doctors had a very good, legitimate reason to recommend a 5-year interval,” he said in an interview.
Dr. Mansour added that no difficulties were encountered in getting patients to agree to a 10-year interval. In his view telephone communication or in-person clinic visits are likely the most effective ways but both are more labor-intensive than automated patient portal messages. “I do not think traditional snail mail is effective.” His clinic uses automatic EMR reminders.
Offering another perspective on the study, Aditya Sreenivasan, MD, a gastroenterologist at Northwell Health in New York City, said his center has not reached out to correct the old intervals. “When I see a patient who previously had a colonoscopy with another physician, I always follow the previous recommendation for when the next colonoscopy should be, regardless of whether or not it technically meets guideline recommendations,” he told this news organization. “I do this because I was not there during the procedure and am not aware of any circumstances that would require a shorter interval that may not be apparent from the report.”
While he agrees with the new guidelines, Dr. Sreenivasan is “not sure if retroactively changing intervals is beneficial to patients, as the presence of guidelines may subconsciously influence the behavior of the endoscopist at the time of the procedure. For example, if a patient has a technically challenging colonoscopy and the endoscopist is running late, the endoscopist may drop their guard once they find a polyp and miss 1-2 additional small polyps that they would have spent more time looking for if they knew their next one would be in 10 years instead of 5.”
As for notification method, despite the logistical downside of taking dedicated staff time to make telephone calls, Dr. Sreenivasan said, “I think having a conversation with the patient directly is a much better way to communicate this information as it allows the patient to ask and answer questions. Things like tone of voice can provide reassurance that one cannot get via email.” Looking to the future, the study authors acknowledged that combinations of initial and reminder outreach approaches — for example, a mailed letter followed by secure message or telephone call — could potentially yield higher response rates and/or adoption rates than they observed. And a longer follow-up period with additional reminders may have produced higher yields. Additional studies are needed to optimize outreach approaches and to understand patient barriers to adopting the new guideline recommendations in different healthcare settings.
The study was supported by a Delivery Science grant from the Kaiser Permanente Northern California.
The authors disclosed no conflicts of interest. Dr. Mansour and Dr. Sreenivasan disclosed no conflicts of interest relevant to their comments.
In an article published in Clinical Gastroenterology and Hepatology, a group led by Jeffrey K. Lee, MD, MPH, a gastroenterologist at Kaiser Permanente Medical Center in San Francisco, reported the following 60-day response rates for the three contact methods in potentially transitioning more than 600 post-polypectomy patients to the new interval:
- Telephone: 64.5%
- Secure messaging: 51.7%
- Mailed letter: 31.3%
Compared with letter outreach, overall rate differences were significant for telephone (18.1%) and secure message outreach (13.1%).
Such interventions are widely used, the authors noted , but have not been compared for efficacy terms of communicating updated colonoscopy intervals.
The trial’s aim was to inform low-risk patients of the recommended interval update from 5 years — used since the 1990s — to 7-10 years. Given a choice, more patients opted to transition to the 10-year surveillance interval in the telephone (37%) and secure messaging arms (32.%) compared with mailed-letter arm (18.9%).
In addition to telephone and secure messaging outreach, factors positively associated with adoption of the 10-year interval were a positive fecal immunochemical test–based index colonoscopy and increasing age. Patients with these characteristics may be biased toward avoiding colonoscopy if not medically necessary, the authors conjectured.
Inversely associated factors included Asian or Pacific Islander race (odds ratio .58), Hispanic ethnicity (OR .40), and a higher Charlson comorbidity score of 2 vs 0 (OR .43).
Possible explanations for the race and ethnicity associations include gaps in culturally component care, lack of engagement with the English-based outreach approaches, and medical mistrust, the authors said.
“In this study, we gave all our patients an option to either extend their surveillance interval to current guideline recommendations or continue with their old interval, and some chose to do that,” Dr. Lee said in an interview. “Patients really appreciated having a choice and to be informed about the latest guideline changes.”
“A critical challenge to health systems is how to effectively de-implement outdated surveillance recommendations for low-risk patients who have a 5-year follow-up interval and potentially transition them to the recommended 7- to 10-year interval,” Dr. Lee and colleagues wrote.
More than 5 million surveillance colonoscopies are performed annually in US patients with a history of adenomas, the main precursor lesion for colorectal cancer, the authors noted.
With the recent guidelines issued in 2020 by the US Multi-Society Task Force on Colorectal Cancer lengthening the follow-up interval to 7-10 years , physicians are being advised to reevaluate low-risk patients previously scheduled with 5-year surveillance and provide an updated recommendation for follow-up.
Study Details
The three-arm pragmatic randomized trial was conducted in low-risk patients 54-70 years of age with one or two small (< 10 mm) tubular adenomas at baseline colonoscopy. Participants due for 5-year surveillance in 2022 were randomly assigned to one of three outreach arms: telephone (n = 200], secure messaging (n = 203), and mailed letter (n = 201). Stratified by age, sex, race, and ethnicity, participants could change their assigned interval to 10 years or continue with their previously scheduled 5-year interval.
As to economic considerations, the authors said that telephone may be the costliest form of outreach in terms of staffing resources. “We don’t know because we did not conduct a formal cost-effectiveness analysis,” Dr. Lee said. “However, we do know phone outreach requires a lot of personnel effort, which is why we also explored the less costly option of secure messaging/email.”
But based on the findings, telephone outreach would be a reasonable approach to update patients on post-polypectomy surveillance guideline changes if secure messaging or text messaging isn’t available, he added.
Downsides to Retroactive Changes?
Commenting on the study but not involved in it, Nabil M. Mansour, MD, an assistant professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, noted that unlike Kaiser Permanente, his center decided against an overall effort to switch patients colonoscopied before the release of the new guidelines over to the new interval.
“Several of our physicians may have chosen to recommend a 5-year interval specifically for a variety of reasons and we felt going back, and making a blanket change to everyone’s interval retrospectively might create confusion and frustration and might actually delay the colonoscopies of some patients for which their doctors had a very good, legitimate reason to recommend a 5-year interval,” he said in an interview.
Dr. Mansour added that no difficulties were encountered in getting patients to agree to a 10-year interval. In his view telephone communication or in-person clinic visits are likely the most effective ways but both are more labor-intensive than automated patient portal messages. “I do not think traditional snail mail is effective.” His clinic uses automatic EMR reminders.
Offering another perspective on the study, Aditya Sreenivasan, MD, a gastroenterologist at Northwell Health in New York City, said his center has not reached out to correct the old intervals. “When I see a patient who previously had a colonoscopy with another physician, I always follow the previous recommendation for when the next colonoscopy should be, regardless of whether or not it technically meets guideline recommendations,” he told this news organization. “I do this because I was not there during the procedure and am not aware of any circumstances that would require a shorter interval that may not be apparent from the report.”
While he agrees with the new guidelines, Dr. Sreenivasan is “not sure if retroactively changing intervals is beneficial to patients, as the presence of guidelines may subconsciously influence the behavior of the endoscopist at the time of the procedure. For example, if a patient has a technically challenging colonoscopy and the endoscopist is running late, the endoscopist may drop their guard once they find a polyp and miss 1-2 additional small polyps that they would have spent more time looking for if they knew their next one would be in 10 years instead of 5.”
As for notification method, despite the logistical downside of taking dedicated staff time to make telephone calls, Dr. Sreenivasan said, “I think having a conversation with the patient directly is a much better way to communicate this information as it allows the patient to ask and answer questions. Things like tone of voice can provide reassurance that one cannot get via email.” Looking to the future, the study authors acknowledged that combinations of initial and reminder outreach approaches — for example, a mailed letter followed by secure message or telephone call — could potentially yield higher response rates and/or adoption rates than they observed. And a longer follow-up period with additional reminders may have produced higher yields. Additional studies are needed to optimize outreach approaches and to understand patient barriers to adopting the new guideline recommendations in different healthcare settings.
The study was supported by a Delivery Science grant from the Kaiser Permanente Northern California.
The authors disclosed no conflicts of interest. Dr. Mansour and Dr. Sreenivasan disclosed no conflicts of interest relevant to their comments.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Cardiorespiratory Fitness May Cut Prostate Cancer Risk
Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.
The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.
“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.
Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.
The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.
There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
Study details
The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.
An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.
According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.
This study was funded by the Swedish Cancer Society. The authors declared no competing interests.
Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.
The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.
“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.
Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.
The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.
There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
Study details
The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.
An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.
According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.
This study was funded by the Swedish Cancer Society. The authors declared no competing interests.
Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.
The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.
“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.
Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.
The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.
There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
Study details
The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.
An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.
According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.
This study was funded by the Swedish Cancer Society. The authors declared no competing interests.
FROM BRITISH JOURNAL OF SPORTS MEDICINE
Targeting Fetus-derived Gdf15 May Curb Nausea and Vomiting of Pregnancy
, and targeting the hormone prophylactically may reduce this common gestational condition.
This protein acts on the brainstem to cause emesis, and, significantly, a mother’s prior exposure to it determines the degree of NVP severity she will experience, according to international researchers including Marlena Fejzo, PhD, a clinical assistant professor of population and public Health at Keck School of Medicine, University of Southern California, Los Angeles.
“GDF15 is at the mechanistic heart of NVP and HG [hyperemesis gravidarum],” Dr. Fejzo and colleagues wrote in Nature, pointing to the need for preventive and therapeutic strategies.
“My previous research showed an association between variation in the GDF15 gene and nausea and vomiting of pregnancy and HG, and this study takes it one step further by elucidating the mechanism. It confirms that the nausea and vomiting (N/V) hormone GDF15 is a major cause of NVP and HG,” Dr. Fejzo said.
The etiology of NVP remains poorly understood although it affects up to 80% of pregnancies. In the US, its severe form, HG, is the leading cause of hospitalization in early pregnancy and the second-leading reason for pregnancy hospitalization overall.
The immunoassay-based study showed that the majority of GDF15 in maternal blood during pregnancy comes from the fetal part of the placenta, and confirms previous studies reporting higher levels in pregnancies with more severe NVP, said Dr. Fejzo, who is who is a board member of the Hyperemesis Education and Research Foundation.
“However, what was really fascinating and surprising is that prior to pregnancy the women who have more severe NVP symptoms actually have lower levels of the hormone.”
Although the gene variant linked to HG was previously associated with higher circulating levels in maternal blood, counterintuitively, this new research showed that women with abnormally high levels prior to pregnancy have either no or very little NVP, said Dr. Fejzo. “That suggests that in humans higher levels may lead to a desensitization to the high levels of the hormone in pregnancy. Then we also proved that desensitization can occur in a mouse model.”
According to Erin Higgins, MD, a clinical assistant professor of obgyn and reproductive biology at the Cleveland Clinic, Cleveland, Ohio, who was not involved in the study, “This is an exciting finding that may help us to better target treatment of N/V in pregnancy. Factors for NVP have been identified, but to my knowledge there has not been a clear etiology.”
Dr. Higgins cautioned, however, that the GDF15 gene seems important in normal placentation, “so it’s not as simple as blocking the gene or its receptor.” But since preconception exposure to GDF15 might decrease nausea and vomiting once a woman is pregnant, prophylactic treatment may be possible, and metformin has been suggested as a possibility, she said.
The study findings emerged from immunoassays on maternal blood samples collected at about 15 weeks (first trimester and early second trimester), from women with NVP (n = 168) or seen at a hospital for HG (n = 57). Results were compared with those from controls having similar characteristics but no significant symptoms.
Interestingly, GDF15 is also associated with cachexia, a condition similar to HG and characterized by loss of appetite and weight loss, Dr. Fejzo noted. “The hormone can be produced by malignant tumors at levels similar to those seen in pregnancy, and symptoms can be reduced by blocking GDF15 or its receptor, GFRAL. Clinical trials are already underway in cancer patients to test this.”
She is seeking funding to test the impact of increasing GDF15 levels prior to pregnancy in patients who previously experienced HG. “I am confident that desensitizing patients by increasing GDF15 prior to pregnancy and by lowering GDF15 levels during pregnancy will work. But we need to make sure we do safety studies and get the dosing and duration right, and that will take some time.”
Desensitization will need testing first in HG, where the risk for adverse maternal and fetal outcomes is high, so the benefit will outweigh any possible risk of testing medication in pregnancy, she continued. “It will take some time before we get to patients with normal NVP, but I do believe eventually the new findings will result in game-changing therapeutics for the condition.”
Dr. Higgins added, “Even if this isn’t the golden ticket, researchers and clinicians are working toward improvements in the treatment of NVP. We’ve already come a long way in recent years with the development of treatment algorithms and the advent of doxylamine/pyridoxine.”
This study was supported primarily by the Medical Research Council UK and National Institute for Health and Care Research UK, with additional support from various research funding organizations, including Novo Nordisk Foundation.
Dr. Fejzo is a paid consultant for Materna Biosciences and NGM Biopharmaceuticals, and a board member and science adviser for the Hyperemesis Education and Research Foundation.
Numerous study co-authors disclosed financial relationships with private-sector companies, including employment and patent ownership.
Dr. Higgins disclosed no competing interests relevant to her comments but is an instructor for Organon.
, and targeting the hormone prophylactically may reduce this common gestational condition.
This protein acts on the brainstem to cause emesis, and, significantly, a mother’s prior exposure to it determines the degree of NVP severity she will experience, according to international researchers including Marlena Fejzo, PhD, a clinical assistant professor of population and public Health at Keck School of Medicine, University of Southern California, Los Angeles.
“GDF15 is at the mechanistic heart of NVP and HG [hyperemesis gravidarum],” Dr. Fejzo and colleagues wrote in Nature, pointing to the need for preventive and therapeutic strategies.
“My previous research showed an association between variation in the GDF15 gene and nausea and vomiting of pregnancy and HG, and this study takes it one step further by elucidating the mechanism. It confirms that the nausea and vomiting (N/V) hormone GDF15 is a major cause of NVP and HG,” Dr. Fejzo said.
The etiology of NVP remains poorly understood although it affects up to 80% of pregnancies. In the US, its severe form, HG, is the leading cause of hospitalization in early pregnancy and the second-leading reason for pregnancy hospitalization overall.
The immunoassay-based study showed that the majority of GDF15 in maternal blood during pregnancy comes from the fetal part of the placenta, and confirms previous studies reporting higher levels in pregnancies with more severe NVP, said Dr. Fejzo, who is who is a board member of the Hyperemesis Education and Research Foundation.
“However, what was really fascinating and surprising is that prior to pregnancy the women who have more severe NVP symptoms actually have lower levels of the hormone.”
Although the gene variant linked to HG was previously associated with higher circulating levels in maternal blood, counterintuitively, this new research showed that women with abnormally high levels prior to pregnancy have either no or very little NVP, said Dr. Fejzo. “That suggests that in humans higher levels may lead to a desensitization to the high levels of the hormone in pregnancy. Then we also proved that desensitization can occur in a mouse model.”
According to Erin Higgins, MD, a clinical assistant professor of obgyn and reproductive biology at the Cleveland Clinic, Cleveland, Ohio, who was not involved in the study, “This is an exciting finding that may help us to better target treatment of N/V in pregnancy. Factors for NVP have been identified, but to my knowledge there has not been a clear etiology.”
Dr. Higgins cautioned, however, that the GDF15 gene seems important in normal placentation, “so it’s not as simple as blocking the gene or its receptor.” But since preconception exposure to GDF15 might decrease nausea and vomiting once a woman is pregnant, prophylactic treatment may be possible, and metformin has been suggested as a possibility, she said.
The study findings emerged from immunoassays on maternal blood samples collected at about 15 weeks (first trimester and early second trimester), from women with NVP (n = 168) or seen at a hospital for HG (n = 57). Results were compared with those from controls having similar characteristics but no significant symptoms.
Interestingly, GDF15 is also associated with cachexia, a condition similar to HG and characterized by loss of appetite and weight loss, Dr. Fejzo noted. “The hormone can be produced by malignant tumors at levels similar to those seen in pregnancy, and symptoms can be reduced by blocking GDF15 or its receptor, GFRAL. Clinical trials are already underway in cancer patients to test this.”
She is seeking funding to test the impact of increasing GDF15 levels prior to pregnancy in patients who previously experienced HG. “I am confident that desensitizing patients by increasing GDF15 prior to pregnancy and by lowering GDF15 levels during pregnancy will work. But we need to make sure we do safety studies and get the dosing and duration right, and that will take some time.”
Desensitization will need testing first in HG, where the risk for adverse maternal and fetal outcomes is high, so the benefit will outweigh any possible risk of testing medication in pregnancy, she continued. “It will take some time before we get to patients with normal NVP, but I do believe eventually the new findings will result in game-changing therapeutics for the condition.”
Dr. Higgins added, “Even if this isn’t the golden ticket, researchers and clinicians are working toward improvements in the treatment of NVP. We’ve already come a long way in recent years with the development of treatment algorithms and the advent of doxylamine/pyridoxine.”
This study was supported primarily by the Medical Research Council UK and National Institute for Health and Care Research UK, with additional support from various research funding organizations, including Novo Nordisk Foundation.
Dr. Fejzo is a paid consultant for Materna Biosciences and NGM Biopharmaceuticals, and a board member and science adviser for the Hyperemesis Education and Research Foundation.
Numerous study co-authors disclosed financial relationships with private-sector companies, including employment and patent ownership.
Dr. Higgins disclosed no competing interests relevant to her comments but is an instructor for Organon.
, and targeting the hormone prophylactically may reduce this common gestational condition.
This protein acts on the brainstem to cause emesis, and, significantly, a mother’s prior exposure to it determines the degree of NVP severity she will experience, according to international researchers including Marlena Fejzo, PhD, a clinical assistant professor of population and public Health at Keck School of Medicine, University of Southern California, Los Angeles.
“GDF15 is at the mechanistic heart of NVP and HG [hyperemesis gravidarum],” Dr. Fejzo and colleagues wrote in Nature, pointing to the need for preventive and therapeutic strategies.
“My previous research showed an association between variation in the GDF15 gene and nausea and vomiting of pregnancy and HG, and this study takes it one step further by elucidating the mechanism. It confirms that the nausea and vomiting (N/V) hormone GDF15 is a major cause of NVP and HG,” Dr. Fejzo said.
The etiology of NVP remains poorly understood although it affects up to 80% of pregnancies. In the US, its severe form, HG, is the leading cause of hospitalization in early pregnancy and the second-leading reason for pregnancy hospitalization overall.
The immunoassay-based study showed that the majority of GDF15 in maternal blood during pregnancy comes from the fetal part of the placenta, and confirms previous studies reporting higher levels in pregnancies with more severe NVP, said Dr. Fejzo, who is who is a board member of the Hyperemesis Education and Research Foundation.
“However, what was really fascinating and surprising is that prior to pregnancy the women who have more severe NVP symptoms actually have lower levels of the hormone.”
Although the gene variant linked to HG was previously associated with higher circulating levels in maternal blood, counterintuitively, this new research showed that women with abnormally high levels prior to pregnancy have either no or very little NVP, said Dr. Fejzo. “That suggests that in humans higher levels may lead to a desensitization to the high levels of the hormone in pregnancy. Then we also proved that desensitization can occur in a mouse model.”
According to Erin Higgins, MD, a clinical assistant professor of obgyn and reproductive biology at the Cleveland Clinic, Cleveland, Ohio, who was not involved in the study, “This is an exciting finding that may help us to better target treatment of N/V in pregnancy. Factors for NVP have been identified, but to my knowledge there has not been a clear etiology.”
Dr. Higgins cautioned, however, that the GDF15 gene seems important in normal placentation, “so it’s not as simple as blocking the gene or its receptor.” But since preconception exposure to GDF15 might decrease nausea and vomiting once a woman is pregnant, prophylactic treatment may be possible, and metformin has been suggested as a possibility, she said.
The study findings emerged from immunoassays on maternal blood samples collected at about 15 weeks (first trimester and early second trimester), from women with NVP (n = 168) or seen at a hospital for HG (n = 57). Results were compared with those from controls having similar characteristics but no significant symptoms.
Interestingly, GDF15 is also associated with cachexia, a condition similar to HG and characterized by loss of appetite and weight loss, Dr. Fejzo noted. “The hormone can be produced by malignant tumors at levels similar to those seen in pregnancy, and symptoms can be reduced by blocking GDF15 or its receptor, GFRAL. Clinical trials are already underway in cancer patients to test this.”
She is seeking funding to test the impact of increasing GDF15 levels prior to pregnancy in patients who previously experienced HG. “I am confident that desensitizing patients by increasing GDF15 prior to pregnancy and by lowering GDF15 levels during pregnancy will work. But we need to make sure we do safety studies and get the dosing and duration right, and that will take some time.”
Desensitization will need testing first in HG, where the risk for adverse maternal and fetal outcomes is high, so the benefit will outweigh any possible risk of testing medication in pregnancy, she continued. “It will take some time before we get to patients with normal NVP, but I do believe eventually the new findings will result in game-changing therapeutics for the condition.”
Dr. Higgins added, “Even if this isn’t the golden ticket, researchers and clinicians are working toward improvements in the treatment of NVP. We’ve already come a long way in recent years with the development of treatment algorithms and the advent of doxylamine/pyridoxine.”
This study was supported primarily by the Medical Research Council UK and National Institute for Health and Care Research UK, with additional support from various research funding organizations, including Novo Nordisk Foundation.
Dr. Fejzo is a paid consultant for Materna Biosciences and NGM Biopharmaceuticals, and a board member and science adviser for the Hyperemesis Education and Research Foundation.
Numerous study co-authors disclosed financial relationships with private-sector companies, including employment and patent ownership.
Dr. Higgins disclosed no competing interests relevant to her comments but is an instructor for Organon.
FROM NATURE
Maternal Vegan Diet May Be Tied To Lower Birth Weight
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/m2]) 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/m2]) 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/m2]) 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.
FROM ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
Adequate Midlife Protein, Especially From Plants, Tied to Healthy Aging
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.
Study: Early Tecovirimat Stops Mpox Progression in HIV Patients
A new analysis supports using the smallpox antiviral tecovirimat (TPOXX/ST-246) in HIV patients showing the first symptoms of the human smallpox disease mpox (monkeypox), caused by the variola virus.
In a small prospective matched cohort analysis, people with HIV (PWH) and mpox disease who received tecovirimat within 7 days of symptom onset were 13 times less likely to experience progression, compared with PWH not prescribed tecovirimat within that window. In a matched cohort of 112 PWH, mpox disease progression occurred in 5.4% in an early tecovirimat group and in 26.8% in a late- or no-tecovirimat group, for a paired odds ratio of 13.00 (95% CI, 1.71-99.40; P = .002).
“Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement,” wrote a team led by Bruce Aldred, MD, of the Division of Infectious Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta, in JAMA Internal Medicine. Early symptoms of mpox include skin rash and mucosal lesions, along with viral symptoms such as fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes.
As of March 1 of last year, the United States reported more than 30,000 cases, while cases numbered more than 86,000 worldwide.
Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to PWH with mpox during the 2022 epidemic, which disproportionately affected PWH, particularly those with low CD4+ T-cell counts or severe mpox clinical manifestations who needed urgent therapy. Developed to treat smallpox, tecovirimat has antiviral activity against other orthopoxviruses, and has reduced mpox-related morbidity and mortality in animals.
Based on the animal data, approval was granted by the US Food and Drug Administration (FDA) for human mpox treatment. Dr. Aldred and colleagues undertook this cohort analysis in the absence of human data and with the postoutbreak decline in cases impeding recruitment to a full-scale clinical trial.
Study design
The preponderantly Black cohort included 112 PWH diagnosed with mpox at four Atlanta hospitals from June 1 to October 7, 2022. Patients were grouped in an early cohort receiving tecovirimat within 7 days of symptom onset or a no or late cohort (no tecovirimat or treatment more than 7 days after symptom onset. Multivariate logistic regression models identified factors associated with progression, defined as development of at least one severe CDC mpox criterion after symptom day 7.
The cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.
Of 112 PWH, 56 receive early tecovirimat and 56 received no or late treatment. In the early group, the median (interquartile range [IQR]) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black, and 10 (17.9%) were, variously, White, American Indian, Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or of unknown race.
In the late- or no-tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black, and 7 (12.5%) were individuals of other or unknown race. Mpox disease progression occurred in 3 PWH in the early-tecovirimat group and 15 PWH (26.8%) in the late- or no-tecovirimat group.
Dr. Aldred and colleagues acknowledged that more research is needed to confirm the findings and cited several study limitations. These included the small sample size, the preponderance of Black participants, and the possibility that unmatched confounding variables could have led to the observation of fewer cases of severe disease in the early-tecovirimat cohort.
This study was supported by a grant from the Emory Center for AIDS Research. Coauthors reported grants from various institutes at the National Institutes of Health as well as from multiple pharmaceutical companies.
A new analysis supports using the smallpox antiviral tecovirimat (TPOXX/ST-246) in HIV patients showing the first symptoms of the human smallpox disease mpox (monkeypox), caused by the variola virus.
In a small prospective matched cohort analysis, people with HIV (PWH) and mpox disease who received tecovirimat within 7 days of symptom onset were 13 times less likely to experience progression, compared with PWH not prescribed tecovirimat within that window. In a matched cohort of 112 PWH, mpox disease progression occurred in 5.4% in an early tecovirimat group and in 26.8% in a late- or no-tecovirimat group, for a paired odds ratio of 13.00 (95% CI, 1.71-99.40; P = .002).
“Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement,” wrote a team led by Bruce Aldred, MD, of the Division of Infectious Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta, in JAMA Internal Medicine. Early symptoms of mpox include skin rash and mucosal lesions, along with viral symptoms such as fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes.
As of March 1 of last year, the United States reported more than 30,000 cases, while cases numbered more than 86,000 worldwide.
Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to PWH with mpox during the 2022 epidemic, which disproportionately affected PWH, particularly those with low CD4+ T-cell counts or severe mpox clinical manifestations who needed urgent therapy. Developed to treat smallpox, tecovirimat has antiviral activity against other orthopoxviruses, and has reduced mpox-related morbidity and mortality in animals.
Based on the animal data, approval was granted by the US Food and Drug Administration (FDA) for human mpox treatment. Dr. Aldred and colleagues undertook this cohort analysis in the absence of human data and with the postoutbreak decline in cases impeding recruitment to a full-scale clinical trial.
Study design
The preponderantly Black cohort included 112 PWH diagnosed with mpox at four Atlanta hospitals from June 1 to October 7, 2022. Patients were grouped in an early cohort receiving tecovirimat within 7 days of symptom onset or a no or late cohort (no tecovirimat or treatment more than 7 days after symptom onset. Multivariate logistic regression models identified factors associated with progression, defined as development of at least one severe CDC mpox criterion after symptom day 7.
The cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.
Of 112 PWH, 56 receive early tecovirimat and 56 received no or late treatment. In the early group, the median (interquartile range [IQR]) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black, and 10 (17.9%) were, variously, White, American Indian, Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or of unknown race.
In the late- or no-tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black, and 7 (12.5%) were individuals of other or unknown race. Mpox disease progression occurred in 3 PWH in the early-tecovirimat group and 15 PWH (26.8%) in the late- or no-tecovirimat group.
Dr. Aldred and colleagues acknowledged that more research is needed to confirm the findings and cited several study limitations. These included the small sample size, the preponderance of Black participants, and the possibility that unmatched confounding variables could have led to the observation of fewer cases of severe disease in the early-tecovirimat cohort.
This study was supported by a grant from the Emory Center for AIDS Research. Coauthors reported grants from various institutes at the National Institutes of Health as well as from multiple pharmaceutical companies.
A new analysis supports using the smallpox antiviral tecovirimat (TPOXX/ST-246) in HIV patients showing the first symptoms of the human smallpox disease mpox (monkeypox), caused by the variola virus.
In a small prospective matched cohort analysis, people with HIV (PWH) and mpox disease who received tecovirimat within 7 days of symptom onset were 13 times less likely to experience progression, compared with PWH not prescribed tecovirimat within that window. In a matched cohort of 112 PWH, mpox disease progression occurred in 5.4% in an early tecovirimat group and in 26.8% in a late- or no-tecovirimat group, for a paired odds ratio of 13.00 (95% CI, 1.71-99.40; P = .002).
“Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement,” wrote a team led by Bruce Aldred, MD, of the Division of Infectious Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta, in JAMA Internal Medicine. Early symptoms of mpox include skin rash and mucosal lesions, along with viral symptoms such as fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes.
As of March 1 of last year, the United States reported more than 30,000 cases, while cases numbered more than 86,000 worldwide.
Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to PWH with mpox during the 2022 epidemic, which disproportionately affected PWH, particularly those with low CD4+ T-cell counts or severe mpox clinical manifestations who needed urgent therapy. Developed to treat smallpox, tecovirimat has antiviral activity against other orthopoxviruses, and has reduced mpox-related morbidity and mortality in animals.
Based on the animal data, approval was granted by the US Food and Drug Administration (FDA) for human mpox treatment. Dr. Aldred and colleagues undertook this cohort analysis in the absence of human data and with the postoutbreak decline in cases impeding recruitment to a full-scale clinical trial.
Study design
The preponderantly Black cohort included 112 PWH diagnosed with mpox at four Atlanta hospitals from June 1 to October 7, 2022. Patients were grouped in an early cohort receiving tecovirimat within 7 days of symptom onset or a no or late cohort (no tecovirimat or treatment more than 7 days after symptom onset. Multivariate logistic regression models identified factors associated with progression, defined as development of at least one severe CDC mpox criterion after symptom day 7.
The cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.
Of 112 PWH, 56 receive early tecovirimat and 56 received no or late treatment. In the early group, the median (interquartile range [IQR]) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black, and 10 (17.9%) were, variously, White, American Indian, Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or of unknown race.
In the late- or no-tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black, and 7 (12.5%) were individuals of other or unknown race. Mpox disease progression occurred in 3 PWH in the early-tecovirimat group and 15 PWH (26.8%) in the late- or no-tecovirimat group.
Dr. Aldred and colleagues acknowledged that more research is needed to confirm the findings and cited several study limitations. These included the small sample size, the preponderance of Black participants, and the possibility that unmatched confounding variables could have led to the observation of fewer cases of severe disease in the early-tecovirimat cohort.
This study was supported by a grant from the Emory Center for AIDS Research. Coauthors reported grants from various institutes at the National Institutes of Health as well as from multiple pharmaceutical companies.
FROM JAMA INTERNAL MEDICINE
Exercise improves physical and cognitive health in Down syndrome
In the first study of its kind, U.K. and French researchers reported that exercise positively affected physical and cognitive health in persons with Down syndrome. “The findings are significant and offer a crucial challenge to the [Down syndrome] and wider societies,” wrote a team led by Dan Gordon, PhD, associate professor of cardiorespiratory exercise physiology at Anglia Ruskin University in Cambridge, England. “Impact of Prescribed Exercise on the Physical and Cognitive Health of Adults with Down Syndrome: The MinDSets Study” was published in the International Journal of Environmental Research and Public Health.
“Through the simple application of walking, a form of exercise which requires little to no equipment or expense, there were significant increases in cognitive and executive function, reflecting improved capabilities in key attributes of information processing, vigilance, and selective attention,” the researchers wrote.
“Increased cognitive function will help foster increased societal integration and quality of life, which, given that this is the first generation of those with [Down syndrome] to outlive their parents and caregivers, is of importance,” they wrote.
For example, those in an exercise-only intervention arm had an 11.4% improvement on the distance covered in the Six-Minute Walk Test, going from a mean of 498.8 meters before intervention to 522.1 meters afterward. Those in a group that combined group exercise with cognitive training increased the distance walked by 9.9%, or 49.2 meters. Groups that got cognitive training only or no intervention showed no significant changes.
In measures of cognitive function, the exercise group showed a 38% increase in selective attention, with the cognitive and combined groups showing changes for the same measure of 16.5% and 55.3%, respectively. The changes for concentration in the exercise-alone group was 31.5%, while those receiving cognitive training alone or combined exercise plus cognitive training showed improvements in concentration of 21% and 15%, respectively.
Asked why a combination intervention was not superior to exercise alone, Dr. Gordon said in an interview, “Something we’re looking at in the data but can’t fully confirm is that the combined group started to become fatigued due to the double dose of the intervention, and this prevented them in the final tests from doing quite so well as the exercise-alone group. Irrespective of the magnitude of change, any cognitive adaptation observed will be beneficial to this population.”
The evidence for the benefits of exercise on both physical and cognitive health in a non–Down syndrome population are well established, he said, but there were few data on its effect on the Down syndrome population.
One small study showed physical and neurocognitive benefits with resistance training.
“The evidence from previous studies showed increased levels of inactivity and sitting time in Down syndrome individuals compared with non–[Down syndrome] controls, so we hypothesized that exercise, albeit small amounts, would increase their physical fitness,” Dr. Gordon said.
His team also hypothesized that walking would stimulate cognitive development since it requires heightened cognitive engagement compared with inactivity. “What surprised us was the degree of improvement,” Dr. Gordon said.
The process of walking requires the brain to interpret information on a real-time basis from both internal and external cues, he continued. “For most of us this process requires low-level cognitive engagement. However, in the [Down syndrome] population, where motor control is impaired and accompanied by poor muscle tone, walking imposes a heightened cognitive load.” It requires them to concentrate on the action, be aware of their surroundings, and make the right decisions, all of which stimulate areas of the brain that control these functions.
Study details
Eighty-three adult participants were available for final analysis – 67 from North America, 8 from Europe, 5 from Africa, 2 from Asia, and 1 from Australia. The mean age of participants was 27.1 years, 40 were female, and all had caregiver support during the study.
Those unable to visualize information on computer and mobile/tablet screens or to listen to instructions/auditory cues were excluded. All were provided with instructions and a mobile monitoring tool set to record steps completed, distances covered, speeds, and heart rate.
Each was assigned to one of four groups. Exercise intervention-only consisted of 8 weeks of cardiorespiratory exercise defined as either walking or jogging three times a week for 30 minutes. Cognitive training included eight levels (about 20 minutes) of cognitive and executive function exercises six times per week. The combined group completed both the cardiorespiratory and cognitive interventions, while the fourth group acted as controls with no intervention.
According to the authors, the study offers a real-life scenario that can be readily adopted within the Down syndrome community.
This study was commissioned by the Canadian Down Syndrome Society. The authors had no conflicts of interest to declare.
In the first study of its kind, U.K. and French researchers reported that exercise positively affected physical and cognitive health in persons with Down syndrome. “The findings are significant and offer a crucial challenge to the [Down syndrome] and wider societies,” wrote a team led by Dan Gordon, PhD, associate professor of cardiorespiratory exercise physiology at Anglia Ruskin University in Cambridge, England. “Impact of Prescribed Exercise on the Physical and Cognitive Health of Adults with Down Syndrome: The MinDSets Study” was published in the International Journal of Environmental Research and Public Health.
“Through the simple application of walking, a form of exercise which requires little to no equipment or expense, there were significant increases in cognitive and executive function, reflecting improved capabilities in key attributes of information processing, vigilance, and selective attention,” the researchers wrote.
“Increased cognitive function will help foster increased societal integration and quality of life, which, given that this is the first generation of those with [Down syndrome] to outlive their parents and caregivers, is of importance,” they wrote.
For example, those in an exercise-only intervention arm had an 11.4% improvement on the distance covered in the Six-Minute Walk Test, going from a mean of 498.8 meters before intervention to 522.1 meters afterward. Those in a group that combined group exercise with cognitive training increased the distance walked by 9.9%, or 49.2 meters. Groups that got cognitive training only or no intervention showed no significant changes.
In measures of cognitive function, the exercise group showed a 38% increase in selective attention, with the cognitive and combined groups showing changes for the same measure of 16.5% and 55.3%, respectively. The changes for concentration in the exercise-alone group was 31.5%, while those receiving cognitive training alone or combined exercise plus cognitive training showed improvements in concentration of 21% and 15%, respectively.
Asked why a combination intervention was not superior to exercise alone, Dr. Gordon said in an interview, “Something we’re looking at in the data but can’t fully confirm is that the combined group started to become fatigued due to the double dose of the intervention, and this prevented them in the final tests from doing quite so well as the exercise-alone group. Irrespective of the magnitude of change, any cognitive adaptation observed will be beneficial to this population.”
The evidence for the benefits of exercise on both physical and cognitive health in a non–Down syndrome population are well established, he said, but there were few data on its effect on the Down syndrome population.
One small study showed physical and neurocognitive benefits with resistance training.
“The evidence from previous studies showed increased levels of inactivity and sitting time in Down syndrome individuals compared with non–[Down syndrome] controls, so we hypothesized that exercise, albeit small amounts, would increase their physical fitness,” Dr. Gordon said.
His team also hypothesized that walking would stimulate cognitive development since it requires heightened cognitive engagement compared with inactivity. “What surprised us was the degree of improvement,” Dr. Gordon said.
The process of walking requires the brain to interpret information on a real-time basis from both internal and external cues, he continued. “For most of us this process requires low-level cognitive engagement. However, in the [Down syndrome] population, where motor control is impaired and accompanied by poor muscle tone, walking imposes a heightened cognitive load.” It requires them to concentrate on the action, be aware of their surroundings, and make the right decisions, all of which stimulate areas of the brain that control these functions.
Study details
Eighty-three adult participants were available for final analysis – 67 from North America, 8 from Europe, 5 from Africa, 2 from Asia, and 1 from Australia. The mean age of participants was 27.1 years, 40 were female, and all had caregiver support during the study.
Those unable to visualize information on computer and mobile/tablet screens or to listen to instructions/auditory cues were excluded. All were provided with instructions and a mobile monitoring tool set to record steps completed, distances covered, speeds, and heart rate.
Each was assigned to one of four groups. Exercise intervention-only consisted of 8 weeks of cardiorespiratory exercise defined as either walking or jogging three times a week for 30 minutes. Cognitive training included eight levels (about 20 minutes) of cognitive and executive function exercises six times per week. The combined group completed both the cardiorespiratory and cognitive interventions, while the fourth group acted as controls with no intervention.
According to the authors, the study offers a real-life scenario that can be readily adopted within the Down syndrome community.
This study was commissioned by the Canadian Down Syndrome Society. The authors had no conflicts of interest to declare.
In the first study of its kind, U.K. and French researchers reported that exercise positively affected physical and cognitive health in persons with Down syndrome. “The findings are significant and offer a crucial challenge to the [Down syndrome] and wider societies,” wrote a team led by Dan Gordon, PhD, associate professor of cardiorespiratory exercise physiology at Anglia Ruskin University in Cambridge, England. “Impact of Prescribed Exercise on the Physical and Cognitive Health of Adults with Down Syndrome: The MinDSets Study” was published in the International Journal of Environmental Research and Public Health.
“Through the simple application of walking, a form of exercise which requires little to no equipment or expense, there were significant increases in cognitive and executive function, reflecting improved capabilities in key attributes of information processing, vigilance, and selective attention,” the researchers wrote.
“Increased cognitive function will help foster increased societal integration and quality of life, which, given that this is the first generation of those with [Down syndrome] to outlive their parents and caregivers, is of importance,” they wrote.
For example, those in an exercise-only intervention arm had an 11.4% improvement on the distance covered in the Six-Minute Walk Test, going from a mean of 498.8 meters before intervention to 522.1 meters afterward. Those in a group that combined group exercise with cognitive training increased the distance walked by 9.9%, or 49.2 meters. Groups that got cognitive training only or no intervention showed no significant changes.
In measures of cognitive function, the exercise group showed a 38% increase in selective attention, with the cognitive and combined groups showing changes for the same measure of 16.5% and 55.3%, respectively. The changes for concentration in the exercise-alone group was 31.5%, while those receiving cognitive training alone or combined exercise plus cognitive training showed improvements in concentration of 21% and 15%, respectively.
Asked why a combination intervention was not superior to exercise alone, Dr. Gordon said in an interview, “Something we’re looking at in the data but can’t fully confirm is that the combined group started to become fatigued due to the double dose of the intervention, and this prevented them in the final tests from doing quite so well as the exercise-alone group. Irrespective of the magnitude of change, any cognitive adaptation observed will be beneficial to this population.”
The evidence for the benefits of exercise on both physical and cognitive health in a non–Down syndrome population are well established, he said, but there were few data on its effect on the Down syndrome population.
One small study showed physical and neurocognitive benefits with resistance training.
“The evidence from previous studies showed increased levels of inactivity and sitting time in Down syndrome individuals compared with non–[Down syndrome] controls, so we hypothesized that exercise, albeit small amounts, would increase their physical fitness,” Dr. Gordon said.
His team also hypothesized that walking would stimulate cognitive development since it requires heightened cognitive engagement compared with inactivity. “What surprised us was the degree of improvement,” Dr. Gordon said.
The process of walking requires the brain to interpret information on a real-time basis from both internal and external cues, he continued. “For most of us this process requires low-level cognitive engagement. However, in the [Down syndrome] population, where motor control is impaired and accompanied by poor muscle tone, walking imposes a heightened cognitive load.” It requires them to concentrate on the action, be aware of their surroundings, and make the right decisions, all of which stimulate areas of the brain that control these functions.
Study details
Eighty-three adult participants were available for final analysis – 67 from North America, 8 from Europe, 5 from Africa, 2 from Asia, and 1 from Australia. The mean age of participants was 27.1 years, 40 were female, and all had caregiver support during the study.
Those unable to visualize information on computer and mobile/tablet screens or to listen to instructions/auditory cues were excluded. All were provided with instructions and a mobile monitoring tool set to record steps completed, distances covered, speeds, and heart rate.
Each was assigned to one of four groups. Exercise intervention-only consisted of 8 weeks of cardiorespiratory exercise defined as either walking or jogging three times a week for 30 minutes. Cognitive training included eight levels (about 20 minutes) of cognitive and executive function exercises six times per week. The combined group completed both the cardiorespiratory and cognitive interventions, while the fourth group acted as controls with no intervention.
According to the authors, the study offers a real-life scenario that can be readily adopted within the Down syndrome community.
This study was commissioned by the Canadian Down Syndrome Society. The authors had no conflicts of interest to declare.
FROM INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH