Clinician Reviews

Key clinical point: Compared with the control diet, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) reduced the abundance of Bifidobacteria in the colonic microbiome of patients with irritable bowel syndrome (IBS), with no significant impact on other microbiome metrics.

Major finding: Overall, a low FODMAP diet had no clear impact on the microbiome biodiversity, total fecal short-chain fatty acid concentration (P  =  .20), and fecal pH (P  =  .14) compared with the control diet, but it was consistently associated with a reduced abundance of Bifidobacteria in the colonic microbiome.

Study details: Findings are from a systematic review and meta-analysis of 9 randomized controlled trials and 1 secondary publication including 403 patients with IBS who received a low FODMAP or control diet.

Disclosures: This study did not receive any funding. D So declared working in a department benefitting from the sales of a digital application and booklets on a low FODMAP diet.

Source: So D et al. Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: A systematic review with meta-analysis. Am J Clin Nutr. 2022 (Jun 21). Doi:  10.1093/ajcn/nqac176

Key clinical point: Compared with the control diet, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) reduced the abundance of Bifidobacteria in the colonic microbiome of patients with irritable bowel syndrome (IBS), with no significant impact on other microbiome metrics.

Major finding: Overall, a low FODMAP diet had no clear impact on the microbiome biodiversity, total fecal short-chain fatty acid concentration (P  =  .20), and fecal pH (P  =  .14) compared with the control diet, but it was consistently associated with a reduced abundance of Bifidobacteria in the colonic microbiome.

Study details: Findings are from a systematic review and meta-analysis of 9 randomized controlled trials and 1 secondary publication including 403 patients with IBS who received a low FODMAP or control diet.

Disclosures: This study did not receive any funding. D So declared working in a department benefitting from the sales of a digital application and booklets on a low FODMAP diet.

Source: So D et al. Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: A systematic review with meta-analysis. Am J Clin Nutr. 2022 (Jun 21). Doi:  10.1093/ajcn/nqac176

Key clinical point: Compared with the control diet, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) reduced the abundance of Bifidobacteria in the colonic microbiome of patients with irritable bowel syndrome (IBS), with no significant impact on other microbiome metrics.

Major finding: Overall, a low FODMAP diet had no clear impact on the microbiome biodiversity, total fecal short-chain fatty acid concentration (P  =  .20), and fecal pH (P  =  .14) compared with the control diet, but it was consistently associated with a reduced abundance of Bifidobacteria in the colonic microbiome.

Study details: Findings are from a systematic review and meta-analysis of 9 randomized controlled trials and 1 secondary publication including 403 patients with IBS who received a low FODMAP or control diet.

Disclosures: This study did not receive any funding. D So declared working in a department benefitting from the sales of a digital application and booklets on a low FODMAP diet.

Source: So D et al. Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: A systematic review with meta-analysis. Am J Clin Nutr. 2022 (Jun 21). Doi:  10.1093/ajcn/nqac176

Key clinical point: In patients with irritable bowel syndrome with diarrhea (IBS-D), enterosgel vs placebo significantly improved abdominal pain and stool consistency, along with improving global symptoms and demonstrating a favorable safety profile.

Major finding: Significantly higher proportion of patients receiving enterosgel vs placebo showed response for the composite of abdominal pain and stool consistency during at least 4 weeks in the 8-week treatment period (37.4% vs 24.3%; adjusted odds ratio 1.95; P  =  .0020), with significant benefits for bloating (P  =  .0021), urgency (P < .0001), and loperamide use (P  =  .0049), and adequate relief from symptoms (P < .0001) in weeks 1-8. There were no enterosgel-related serious adverse events.

Study details Findings are from a randomized controlled trial including 431 patients with IBS-D who received enterosgel or placebo.

Disclosures: This study was funded by Bioline Products s.r.o. E Markaryan declared being the CEO of Enteromed, the study sponsor. CA Howell declared being an employee of Enteromed. The other authors declared being subcontracted by the sponsor or serving as chief investigator or trial steering committee members.

Source: Howell CA et al. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). Gut. 2022 (Jun 27). Doi: 10.1136/gutjnl-2022-327293

Key clinical point: In patients with irritable bowel syndrome with diarrhea (IBS-D), enterosgel vs placebo significantly improved abdominal pain and stool consistency, along with improving global symptoms and demonstrating a favorable safety profile.

Major finding: Significantly higher proportion of patients receiving enterosgel vs placebo showed response for the composite of abdominal pain and stool consistency during at least 4 weeks in the 8-week treatment period (37.4% vs 24.3%; adjusted odds ratio 1.95; P  =  .0020), with significant benefits for bloating (P  =  .0021), urgency (P < .0001), and loperamide use (P  =  .0049), and adequate relief from symptoms (P < .0001) in weeks 1-8. There were no enterosgel-related serious adverse events.

Study details Findings are from a randomized controlled trial including 431 patients with IBS-D who received enterosgel or placebo.

Disclosures: This study was funded by Bioline Products s.r.o. E Markaryan declared being the CEO of Enteromed, the study sponsor. CA Howell declared being an employee of Enteromed. The other authors declared being subcontracted by the sponsor or serving as chief investigator or trial steering committee members.

Source: Howell CA et al. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). Gut. 2022 (Jun 27). Doi: 10.1136/gutjnl-2022-327293

Key clinical point: In patients with irritable bowel syndrome with diarrhea (IBS-D), enterosgel vs placebo significantly improved abdominal pain and stool consistency, along with improving global symptoms and demonstrating a favorable safety profile.

Major finding: Significantly higher proportion of patients receiving enterosgel vs placebo showed response for the composite of abdominal pain and stool consistency during at least 4 weeks in the 8-week treatment period (37.4% vs 24.3%; adjusted odds ratio 1.95; P  =  .0020), with significant benefits for bloating (P  =  .0021), urgency (P < .0001), and loperamide use (P  =  .0049), and adequate relief from symptoms (P < .0001) in weeks 1-8. There were no enterosgel-related serious adverse events.

Study details Findings are from a randomized controlled trial including 431 patients with IBS-D who received enterosgel or placebo.

Disclosures: This study was funded by Bioline Products s.r.o. E Markaryan declared being the CEO of Enteromed, the study sponsor. CA Howell declared being an employee of Enteromed. The other authors declared being subcontracted by the sponsor or serving as chief investigator or trial steering committee members.

Source: Howell CA et al. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). Gut. 2022 (Jun 27). Doi: 10.1136/gutjnl-2022-327293

Key clinical point: Transcutaneous electrical acustimulation (TEA) at the ST36 and PC6 acupuncture points improved symptoms of constipation and abdominal pain in patients with irritable bowel syndrome with constipation (IBS-C).

Major finding: The number of complete spontaneous bowel movements (CSBM) per week during the fourth week of treatment was significantly higher in the TEA vs sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6; P  =  .002), with 44.0% vs 4.2% of patients reporting ≥3 CSBM/week (P  =  .001). TEA led to significant improvements in visual analog scale pain score (P  =  .002) and IBS-Severity Scoring System score (P  =  .025).

Study details: Findings are from a randomized controlled trial including 52 patients with IBS-C who were randomly assigned to receive either TEA or sham-TEA daily for 4 weeks.

Disclosures: This study was funded by the National Natural Science Foundation of China and Zhejiang Medical and Health Science and Technology Project. The authors declared no conflicts of interest.

Source: Huang Z et al. Transcutaneous electrical acustimulation improves irritable bowel syndrome with constipation by accelerating colon transit and reducing rectal sensation via autonomic mechanisms. Am J Gastroenterol. 2022 (Jun 17). Doi:  10.14309/ajg.0000000000001882

Key clinical point: Transcutaneous electrical acustimulation (TEA) at the ST36 and PC6 acupuncture points improved symptoms of constipation and abdominal pain in patients with irritable bowel syndrome with constipation (IBS-C).

Major finding: The number of complete spontaneous bowel movements (CSBM) per week during the fourth week of treatment was significantly higher in the TEA vs sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6; P  =  .002), with 44.0% vs 4.2% of patients reporting ≥3 CSBM/week (P  =  .001). TEA led to significant improvements in visual analog scale pain score (P  =  .002) and IBS-Severity Scoring System score (P  =  .025).

Study details: Findings are from a randomized controlled trial including 52 patients with IBS-C who were randomly assigned to receive either TEA or sham-TEA daily for 4 weeks.

Disclosures: This study was funded by the National Natural Science Foundation of China and Zhejiang Medical and Health Science and Technology Project. The authors declared no conflicts of interest.

Source: Huang Z et al. Transcutaneous electrical acustimulation improves irritable bowel syndrome with constipation by accelerating colon transit and reducing rectal sensation via autonomic mechanisms. Am J Gastroenterol. 2022 (Jun 17). Doi:  10.14309/ajg.0000000000001882

Key clinical point: Transcutaneous electrical acustimulation (TEA) at the ST36 and PC6 acupuncture points improved symptoms of constipation and abdominal pain in patients with irritable bowel syndrome with constipation (IBS-C).

Major finding: The number of complete spontaneous bowel movements (CSBM) per week during the fourth week of treatment was significantly higher in the TEA vs sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6; P  =  .002), with 44.0% vs 4.2% of patients reporting ≥3 CSBM/week (P  =  .001). TEA led to significant improvements in visual analog scale pain score (P  =  .002) and IBS-Severity Scoring System score (P  =  .025).

Study details: Findings are from a randomized controlled trial including 52 patients with IBS-C who were randomly assigned to receive either TEA or sham-TEA daily for 4 weeks.

Disclosures: This study was funded by the National Natural Science Foundation of China and Zhejiang Medical and Health Science and Technology Project. The authors declared no conflicts of interest.

Source: Huang Z et al. Transcutaneous electrical acustimulation improves irritable bowel syndrome with constipation by accelerating colon transit and reducing rectal sensation via autonomic mechanisms. Am J Gastroenterol. 2022 (Jun 17). Doi:  10.14309/ajg.0000000000001882

Key clinical point: Fecal microbiota transplantation (FMT) was safe and effective with effects sustained for at least 3 years after transplantation in patients with irritable bowel syndrome (IBS).

Major finding: Patients who received 30 or 60 g feces vs placebo showed a significantly higher response rate and significantly lower IBS-Severity Scoring System scores at 2 and 3 years after FMT (all P ≤ .05). No adverse event other than mild intermittent abdominal pain, diarrhea, and constipation within the first 2 days after FMT were reported.

Study details: Findings are from a 3-year follow-up study of 125 patients with IBS who underwent FMT and were randomly assigned to receive placebo (own feces) or donor feces (30 or 60 g); feces were administered to the duodenum.

Disclosures: This study was supported by Helse Fonna. The authors declared no conflicts of interest.

Source: El-Salhy M et al. Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation. Gastroenterology. 2022 (Jun 13). Doi:  10.1053/j.gastro.2022.06.020

Key clinical point: Fecal microbiota transplantation (FMT) was safe and effective with effects sustained for at least 3 years after transplantation in patients with irritable bowel syndrome (IBS).

Major finding: Patients who received 30 or 60 g feces vs placebo showed a significantly higher response rate and significantly lower IBS-Severity Scoring System scores at 2 and 3 years after FMT (all P ≤ .05). No adverse event other than mild intermittent abdominal pain, diarrhea, and constipation within the first 2 days after FMT were reported.

Study details: Findings are from a 3-year follow-up study of 125 patients with IBS who underwent FMT and were randomly assigned to receive placebo (own feces) or donor feces (30 or 60 g); feces were administered to the duodenum.

Disclosures: This study was supported by Helse Fonna. The authors declared no conflicts of interest.

Source: El-Salhy M et al. Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation. Gastroenterology. 2022 (Jun 13). Doi:  10.1053/j.gastro.2022.06.020

Key clinical point: Fecal microbiota transplantation (FMT) was safe and effective with effects sustained for at least 3 years after transplantation in patients with irritable bowel syndrome (IBS).

Major finding: Patients who received 30 or 60 g feces vs placebo showed a significantly higher response rate and significantly lower IBS-Severity Scoring System scores at 2 and 3 years after FMT (all P ≤ .05). No adverse event other than mild intermittent abdominal pain, diarrhea, and constipation within the first 2 days after FMT were reported.

Study details: Findings are from a 3-year follow-up study of 125 patients with IBS who underwent FMT and were randomly assigned to receive placebo (own feces) or donor feces (30 or 60 g); feces were administered to the duodenum.

Disclosures: This study was supported by Helse Fonna. The authors declared no conflicts of interest.

Source: El-Salhy M et al. Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation. Gastroenterology. 2022 (Jun 13). Doi:  10.1053/j.gastro.2022.06.020

INDIANAPOLIS – When adolescents present with acne that is not responding to isotretinoin, make sure to ask if they’re taking the medication when eating fatty food – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.

“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.

Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.

If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.

Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.

In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”

The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.

“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”

Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.

Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.

“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”

Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”

Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.

INDIANAPOLIS – When adolescents present with acne that is not responding to isotretinoin, make sure to ask if they’re taking the medication when eating fatty food – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.

“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.

Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.

If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.

Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.

In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”

The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.

“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”

Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.

Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.

“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”

Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”

Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.

INDIANAPOLIS – When adolescents present with acne that is not responding to isotretinoin, make sure to ask if they’re taking the medication when eating fatty food – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.

“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.

Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.

If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.

Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.

In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”

The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.

“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”

Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.

Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.

“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”

Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”

Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Drinks sweetened with sugar – but not natural juices or drinks sweetened artificially – were linked to a higher risk of inflammatory bowel disease (IBD) in people who drank more than one a day in a study of more than 120,000 people.

IBD has previously been linked with high consumption of sugar, but population-based evidence has been inconclusive, and natural juices have not been studied, write lead author Tian Fu, with the department of gastroenterology, the Third Xiangya Hospital of Central South University in Changsha, China, and colleagues.

Their study compared the associations of sugar-sweetened drinks, artificially sweetened beverages, and natural juices (including pure fruit or vegetable juices) with IBD risk.

“As one of the major sources of free sugar, beverages have been related to inflammation-related health outcomes but received less attention in the field of IBD,” the authors wrote.

“Our findings, if proven causal, suggest reduced consumption of sugar-sweetened beverages as a strategy for prevention of IBD, especially Crohn’s disease (CD), but further studies are needed to confirm these findings and explore the underlying mechanism,” they write.

The study was published online in Alimentary Pharmacology and Therapeutics.
 

Link significant for Crohn’s disease but not ulcerative colitis

The researchers used data from 121,490 participants in the UK Biobank who did not have IBD at trial recruitment in 2006-2010. The average age of the participants was 56 years, and almost all (96.9%) were White. The researchers studied their intake of beverages with 24-hour diet recalls from 2009 to 2012.

Participants were sorted into three groups according to the consumption of each beverage: 0 unit (glasses, cans, or 250 mL/cartons) per day (reference group), 0-1 unit per day, and more than 1 unit per day.

While most (66.3%) did not drink any sugar-sweetened beverages, participants who reported drinking more than 1 unit per day were more likely to have a higher body mass index and consume higher amounts of total energy and sugar.

During an average follow-up of about 10 years, the investigators documented 510 incident IBD cases: 143 cases of CD and 367 cases of ulcerative colitis (UC).

Compared to people who did not drink sugar-sweetened beverages, those who drank at least 1 unit per day had a significantly higher IBD risk (hazard ratio, 1.51; 95% confidence interval, 1.11-2.05), but the trend was statistically nonsignificant.

The association was significant for CD (HR, 2.05; 95% CI, 1.22,3.46) but not for UC (HR, 1.31; 95% CI, 0.89-1.92). The positive association between sugar-sweetened drinks and risk of CD, but not UC, was in line with previous studies showing that dietary patterns were more associated with CD risk, the authors noted.

They also highlighted that there was no positive link between artificially sweetened beverages, natural juices, or total sugar intake and IBD risk. They noted that the inflammatory role of artificial sweeteners is still being debated.

Additionally, the effect of natural sugar in juices may be counteracted by fiber and bioactive compounds in the juices, the authors wrote.

A limitation of the study is that at baseline, all participants in the UK Biobank were older than 40 years, so the researchers could not examine any links with younger-onset IBD.

Additionally, the self-reported questionnaires are subject to recall bias, though the survey has been validated.
 

Study adds to previous evidence

Hasan Zaki, PhD, an assistant professor with the department of pathology at University of Texas Southwestern Medical Center, Dallas, said in an interview that the size of this population-based study adds evidence that simple sugar can increase the risk for IBD. Dr. Zaki studies the relationship of inflammatory disorders and diet and was not involved in the study.

“This study is very strong evidence of the association between high sugar and IBD,” he said. He noted that more studies are needed because there are few studies in this area and results have varied.

His lab conducted work on the subject previously in mice. In a 2020 study, they found that a high-sugar diet helped promote IBD development and gut microbiota dysfunction.

Dr. Zaki pointed out that, among people in the United Kingdom and those in the United States, diets, demographics, and IBD incidence are similar, a fact that may make the findings more generalizable.

However, studies comparing the categories of sweetened drinks should be conducted in a U.S. population to assess the results in a diverse group to see whether ethnicity plays a role, because almost all of the people in the UK group were White, he said.

Also important, Dr. Zaki said, will be follow-up studies of the link between sweet drinks and IBD in U.S. children, among whom consumption is particularly high and the IBD incidence is rising. One study showed the prevalence increased 133% from 2007 to 2016.

The results of this study should help gastroenterologists counsel patients on an ideal diet to avoid IBD or reduce IBD severity, he said.

The study was supported by the National Natural Science Foundation of China and Key Project of Research and Development Plan of Hunan Province. The study authors and Dr. Zaki report no relevant financial relationships.

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

Drinks sweetened with sugar – but not natural juices or drinks sweetened artificially – were linked to a higher risk of inflammatory bowel disease (IBD) in people who drank more than one a day in a study of more than 120,000 people.

IBD has previously been linked with high consumption of sugar, but population-based evidence has been inconclusive, and natural juices have not been studied, write lead author Tian Fu, with the department of gastroenterology, the Third Xiangya Hospital of Central South University in Changsha, China, and colleagues.

Their study compared the associations of sugar-sweetened drinks, artificially sweetened beverages, and natural juices (including pure fruit or vegetable juices) with IBD risk.

“As one of the major sources of free sugar, beverages have been related to inflammation-related health outcomes but received less attention in the field of IBD,” the authors wrote.

“Our findings, if proven causal, suggest reduced consumption of sugar-sweetened beverages as a strategy for prevention of IBD, especially Crohn’s disease (CD), but further studies are needed to confirm these findings and explore the underlying mechanism,” they write.

The study was published online in Alimentary Pharmacology and Therapeutics.
 

Link significant for Crohn’s disease but not ulcerative colitis

The researchers used data from 121,490 participants in the UK Biobank who did not have IBD at trial recruitment in 2006-2010. The average age of the participants was 56 years, and almost all (96.9%) were White. The researchers studied their intake of beverages with 24-hour diet recalls from 2009 to 2012.

Participants were sorted into three groups according to the consumption of each beverage: 0 unit (glasses, cans, or 250 mL/cartons) per day (reference group), 0-1 unit per day, and more than 1 unit per day.

While most (66.3%) did not drink any sugar-sweetened beverages, participants who reported drinking more than 1 unit per day were more likely to have a higher body mass index and consume higher amounts of total energy and sugar.

During an average follow-up of about 10 years, the investigators documented 510 incident IBD cases: 143 cases of CD and 367 cases of ulcerative colitis (UC).

Compared to people who did not drink sugar-sweetened beverages, those who drank at least 1 unit per day had a significantly higher IBD risk (hazard ratio, 1.51; 95% confidence interval, 1.11-2.05), but the trend was statistically nonsignificant.

The association was significant for CD (HR, 2.05; 95% CI, 1.22,3.46) but not for UC (HR, 1.31; 95% CI, 0.89-1.92). The positive association between sugar-sweetened drinks and risk of CD, but not UC, was in line with previous studies showing that dietary patterns were more associated with CD risk, the authors noted.

They also highlighted that there was no positive link between artificially sweetened beverages, natural juices, or total sugar intake and IBD risk. They noted that the inflammatory role of artificial sweeteners is still being debated.

Additionally, the effect of natural sugar in juices may be counteracted by fiber and bioactive compounds in the juices, the authors wrote.

A limitation of the study is that at baseline, all participants in the UK Biobank were older than 40 years, so the researchers could not examine any links with younger-onset IBD.

Additionally, the self-reported questionnaires are subject to recall bias, though the survey has been validated.
 

Study adds to previous evidence

Hasan Zaki, PhD, an assistant professor with the department of pathology at University of Texas Southwestern Medical Center, Dallas, said in an interview that the size of this population-based study adds evidence that simple sugar can increase the risk for IBD. Dr. Zaki studies the relationship of inflammatory disorders and diet and was not involved in the study.

“This study is very strong evidence of the association between high sugar and IBD,” he said. He noted that more studies are needed because there are few studies in this area and results have varied.

His lab conducted work on the subject previously in mice. In a 2020 study, they found that a high-sugar diet helped promote IBD development and gut microbiota dysfunction.

Dr. Zaki pointed out that, among people in the United Kingdom and those in the United States, diets, demographics, and IBD incidence are similar, a fact that may make the findings more generalizable.

However, studies comparing the categories of sweetened drinks should be conducted in a U.S. population to assess the results in a diverse group to see whether ethnicity plays a role, because almost all of the people in the UK group were White, he said.

Also important, Dr. Zaki said, will be follow-up studies of the link between sweet drinks and IBD in U.S. children, among whom consumption is particularly high and the IBD incidence is rising. One study showed the prevalence increased 133% from 2007 to 2016.

The results of this study should help gastroenterologists counsel patients on an ideal diet to avoid IBD or reduce IBD severity, he said.

The study was supported by the National Natural Science Foundation of China and Key Project of Research and Development Plan of Hunan Province. The study authors and Dr. Zaki report no relevant financial relationships.

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

Drinks sweetened with sugar – but not natural juices or drinks sweetened artificially – were linked to a higher risk of inflammatory bowel disease (IBD) in people who drank more than one a day in a study of more than 120,000 people.

IBD has previously been linked with high consumption of sugar, but population-based evidence has been inconclusive, and natural juices have not been studied, write lead author Tian Fu, with the department of gastroenterology, the Third Xiangya Hospital of Central South University in Changsha, China, and colleagues.

Their study compared the associations of sugar-sweetened drinks, artificially sweetened beverages, and natural juices (including pure fruit or vegetable juices) with IBD risk.

“As one of the major sources of free sugar, beverages have been related to inflammation-related health outcomes but received less attention in the field of IBD,” the authors wrote.

“Our findings, if proven causal, suggest reduced consumption of sugar-sweetened beverages as a strategy for prevention of IBD, especially Crohn’s disease (CD), but further studies are needed to confirm these findings and explore the underlying mechanism,” they write.

The study was published online in Alimentary Pharmacology and Therapeutics.
 

Link significant for Crohn’s disease but not ulcerative colitis

The researchers used data from 121,490 participants in the UK Biobank who did not have IBD at trial recruitment in 2006-2010. The average age of the participants was 56 years, and almost all (96.9%) were White. The researchers studied their intake of beverages with 24-hour diet recalls from 2009 to 2012.

Participants were sorted into three groups according to the consumption of each beverage: 0 unit (glasses, cans, or 250 mL/cartons) per day (reference group), 0-1 unit per day, and more than 1 unit per day.

While most (66.3%) did not drink any sugar-sweetened beverages, participants who reported drinking more than 1 unit per day were more likely to have a higher body mass index and consume higher amounts of total energy and sugar.

During an average follow-up of about 10 years, the investigators documented 510 incident IBD cases: 143 cases of CD and 367 cases of ulcerative colitis (UC).

Compared to people who did not drink sugar-sweetened beverages, those who drank at least 1 unit per day had a significantly higher IBD risk (hazard ratio, 1.51; 95% confidence interval, 1.11-2.05), but the trend was statistically nonsignificant.

The association was significant for CD (HR, 2.05; 95% CI, 1.22,3.46) but not for UC (HR, 1.31; 95% CI, 0.89-1.92). The positive association between sugar-sweetened drinks and risk of CD, but not UC, was in line with previous studies showing that dietary patterns were more associated with CD risk, the authors noted.

They also highlighted that there was no positive link between artificially sweetened beverages, natural juices, or total sugar intake and IBD risk. They noted that the inflammatory role of artificial sweeteners is still being debated.

Additionally, the effect of natural sugar in juices may be counteracted by fiber and bioactive compounds in the juices, the authors wrote.

A limitation of the study is that at baseline, all participants in the UK Biobank were older than 40 years, so the researchers could not examine any links with younger-onset IBD.

Additionally, the self-reported questionnaires are subject to recall bias, though the survey has been validated.
 

Study adds to previous evidence

Hasan Zaki, PhD, an assistant professor with the department of pathology at University of Texas Southwestern Medical Center, Dallas, said in an interview that the size of this population-based study adds evidence that simple sugar can increase the risk for IBD. Dr. Zaki studies the relationship of inflammatory disorders and diet and was not involved in the study.

“This study is very strong evidence of the association between high sugar and IBD,” he said. He noted that more studies are needed because there are few studies in this area and results have varied.

His lab conducted work on the subject previously in mice. In a 2020 study, they found that a high-sugar diet helped promote IBD development and gut microbiota dysfunction.

Dr. Zaki pointed out that, among people in the United Kingdom and those in the United States, diets, demographics, and IBD incidence are similar, a fact that may make the findings more generalizable.

However, studies comparing the categories of sweetened drinks should be conducted in a U.S. population to assess the results in a diverse group to see whether ethnicity plays a role, because almost all of the people in the UK group were White, he said.

Also important, Dr. Zaki said, will be follow-up studies of the link between sweet drinks and IBD in U.S. children, among whom consumption is particularly high and the IBD incidence is rising. One study showed the prevalence increased 133% from 2007 to 2016.

The results of this study should help gastroenterologists counsel patients on an ideal diet to avoid IBD or reduce IBD severity, he said.

The study was supported by the National Natural Science Foundation of China and Key Project of Research and Development Plan of Hunan Province. The study authors and Dr. Zaki report no relevant financial relationships.

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

Susan Snead used to live in an apartment complex for older adults. The complex had a nice dayroom, and neighbors would knock on her door every now and then to check in.

But despite not being lonely, Ms. Snead, 89, did live alone in downtown Charleston, S.C. Eventually, that became dangerous.

“I fell a few times,” she says. “I had to call somebody to come and get me up.”

Sometimes help would come from the apartment complex’s office. Sometimes it came with a police escort.

Over time, needing to make those calls became a burden. Making and keeping appointments with her doctor, something she had to do regularly, as she has diabetes, got harder, too.

“It kind of wore me out,” she says. “Like you’re going up a hill.”

As she was beginning to accept she could no longer live alone, Ms. Snead, an Air Force veteran, learned about a program run by the Department of Veterans Affairs called Medical Foster Home.

Medical foster homes are privately owned homes in which a licensed caregiver lives with and supervises residents around the clock. Caregivers help aging veterans with activities of daily living like bathing, cooking, making and getting to appointments, getting dressed, and taking daily medication.

Caregivers can take care of up to three residents in their home at a time. While most residents are veterans, caregivers sometimes care for non-veteran residents, such as a veteran’s spouse or a caregiver’s family member.

Veterans typically pay about $1,500 to $3,000 out-of-pocket per month for the service, depending on location.

According to the VA, the concept of medical foster homes has been around since 1999, when VA hospitals across the country began reaching out to people willing to provide live-in care for veterans. The option is led by local VA hospitals, which approve caregivers and provide administrative services. There are now 517 medical foster homes, the VA says.

Much like other residential care facilities, medical foster homes get regular inspections for safety, nutrition, and more.

In 2019, Ms. Snead signed up for the program. She expected to be cared for, but she found a sense of family with her caregiver, Wilhelmina Brown, and another veteran in the home.

Ms. Brown started taking care of people – but not necessarily veterans – in 1997 when her grandmother was unable to care for herself, she says.

“My grandmama carried me to church every Sunday, she carried me to the beach – everywhere she went, she took me with her,” Ms. Brown says. As her grandmother got older, “I said, ‘I’m going to take care of her in my home.’ ”

Caring for others must come from the heart, Ms. Brown says.

She cooks her residents’ meals three times a day with dietary restrictions in mind, washes their dishes, does their laundry, remembers birthdays, and plans little parties.

“That’s my family,” Ms. Brown says.

In 2020, the COVID-19 pandemic upended the world – but at the same time, it highlighted the advantages of the medical foster home model.

Home-based primary care keeps veterans out of nursing homes – something that became particularly important as COVID-19 hit nursing homes and long-term care facilities.

Caregivers in the system were also able to help veterans, often living in rural areas, pivot and adapt to telehealth during a time of crisis.

One study, published in the journal Geriatrics, set out to identify how medical foster homes were able to deliver safe, effective health care during the early stages of the pandemic.

Researchers interviewed 37 VA care providers at 16 rural medical foster home programs across the country. The interviews took place between December 2020 and February 2021. They found medical foster home caregivers, coordinators, and health care providers communicated to move office visits to the home, helped veterans navigate telehealth, advocated to get veterans vaccinated in-home, and relied on each other to fight social isolation.

Caregivers also adapted quickly to telehealth, according to Leah Haverhals, PhD, a health research scientist and communications director for the Seattle-Denver Center of Innovation for Veteran Centered and Value Driven Care, who led the study.

Most veterans in the foster home program are older and find new technology difficult to use.

Caregivers, coordinators, and health care providers were largely new to the technology, too.

While the study found that most veterans and caregivers preferred in-person care, they were able to work together to make the best of telehealth.

“That speaks to the nature of the care being given, being able to pivot in a crisis like that,” Dr. Haverhals says.

If caregivers didn’t already have computers or telehealth-compatible devices, the VA provided iPads that would connect to the internet using cellular signals. According to the study, this helped to overcome connectivity issues that may have caused problems in rural areas.

Ms. Snead says Ms. Brown helped a lot with her telehealth calls.

“If we had to do things over the phone or with video, she was able to set that up to work with the person on the other end. She knows a lot about that stuff – about computers and things like that,” Ms. Snead says, adding that she hadn’t worked with computers since retirement in 1998.

Telehealth helped health care providers identify infections and quickly prescribe antibiotics to veterans in rural areas and provide other care that was more safely delivered in private homes.

“The findings from our study highlighted that when working together for the common goal of keeping vulnerable populations like veterans in MFHs [medical foster homes] safe during times of crisis, adaptation and collaboration facilitated the ongoing provision of high-quality care,” Dr. Haverhals’s group wrote. “Such collaboration has been shown to be critical in recent research in the United States on supporting older adults during the pandemic.”

Cari Levy, MD, PhD, a professor at the University of Colorado at Denver, Aurora, and a co-author of the study, specializes in palliative and telenursing home care for the VA.

Dr. Levy, who has worked for the VA for about 20 years, says how medical foster homes provided care during the pandemic carries lessons for civilian clinics. One of the most important lessons, she says, is that medical professionals will need to provide more care where people are, especially in populations that are too sick to get to the clinic.

“For years, there was all this hope that telehealth would expand,” but it took a pandemic to authorize approval from federal agencies to explode, she says. “I shudder to think what would have happened if we didn’t have telehealth. Fortunately, it was the right time to be able to flip a switch.”

Crisis aside, Dr. Levy says her dream would be for health care providers to do more home-based care. The model allows people to preserve the relational aspects of medicine, which can counteract a lot of the moral injury and burnout in the field, she says, adding:

“I see this as the kind of medicine many people intended to do when they got into medicine.”

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

Susan Snead used to live in an apartment complex for older adults. The complex had a nice dayroom, and neighbors would knock on her door every now and then to check in.

But despite not being lonely, Ms. Snead, 89, did live alone in downtown Charleston, S.C. Eventually, that became dangerous.

“I fell a few times,” she says. “I had to call somebody to come and get me up.”

Sometimes help would come from the apartment complex’s office. Sometimes it came with a police escort.

Over time, needing to make those calls became a burden. Making and keeping appointments with her doctor, something she had to do regularly, as she has diabetes, got harder, too.

“It kind of wore me out,” she says. “Like you’re going up a hill.”

As she was beginning to accept she could no longer live alone, Ms. Snead, an Air Force veteran, learned about a program run by the Department of Veterans Affairs called Medical Foster Home.

Medical foster homes are privately owned homes in which a licensed caregiver lives with and supervises residents around the clock. Caregivers help aging veterans with activities of daily living like bathing, cooking, making and getting to appointments, getting dressed, and taking daily medication.

Caregivers can take care of up to three residents in their home at a time. While most residents are veterans, caregivers sometimes care for non-veteran residents, such as a veteran’s spouse or a caregiver’s family member.

Veterans typically pay about $1,500 to $3,000 out-of-pocket per month for the service, depending on location.

According to the VA, the concept of medical foster homes has been around since 1999, when VA hospitals across the country began reaching out to people willing to provide live-in care for veterans. The option is led by local VA hospitals, which approve caregivers and provide administrative services. There are now 517 medical foster homes, the VA says.

Much like other residential care facilities, medical foster homes get regular inspections for safety, nutrition, and more.

In 2019, Ms. Snead signed up for the program. She expected to be cared for, but she found a sense of family with her caregiver, Wilhelmina Brown, and another veteran in the home.

Ms. Brown started taking care of people – but not necessarily veterans – in 1997 when her grandmother was unable to care for herself, she says.

“My grandmama carried me to church every Sunday, she carried me to the beach – everywhere she went, she took me with her,” Ms. Brown says. As her grandmother got older, “I said, ‘I’m going to take care of her in my home.’ ”

Caring for others must come from the heart, Ms. Brown says.

She cooks her residents’ meals three times a day with dietary restrictions in mind, washes their dishes, does their laundry, remembers birthdays, and plans little parties.

“That’s my family,” Ms. Brown says.

In 2020, the COVID-19 pandemic upended the world – but at the same time, it highlighted the advantages of the medical foster home model.

Home-based primary care keeps veterans out of nursing homes – something that became particularly important as COVID-19 hit nursing homes and long-term care facilities.

Caregivers in the system were also able to help veterans, often living in rural areas, pivot and adapt to telehealth during a time of crisis.

One study, published in the journal Geriatrics, set out to identify how medical foster homes were able to deliver safe, effective health care during the early stages of the pandemic.

Researchers interviewed 37 VA care providers at 16 rural medical foster home programs across the country. The interviews took place between December 2020 and February 2021. They found medical foster home caregivers, coordinators, and health care providers communicated to move office visits to the home, helped veterans navigate telehealth, advocated to get veterans vaccinated in-home, and relied on each other to fight social isolation.

Caregivers also adapted quickly to telehealth, according to Leah Haverhals, PhD, a health research scientist and communications director for the Seattle-Denver Center of Innovation for Veteran Centered and Value Driven Care, who led the study.

Most veterans in the foster home program are older and find new technology difficult to use.

Caregivers, coordinators, and health care providers were largely new to the technology, too.

While the study found that most veterans and caregivers preferred in-person care, they were able to work together to make the best of telehealth.

“That speaks to the nature of the care being given, being able to pivot in a crisis like that,” Dr. Haverhals says.

If caregivers didn’t already have computers or telehealth-compatible devices, the VA provided iPads that would connect to the internet using cellular signals. According to the study, this helped to overcome connectivity issues that may have caused problems in rural areas.

Ms. Snead says Ms. Brown helped a lot with her telehealth calls.

“If we had to do things over the phone or with video, she was able to set that up to work with the person on the other end. She knows a lot about that stuff – about computers and things like that,” Ms. Snead says, adding that she hadn’t worked with computers since retirement in 1998.

Telehealth helped health care providers identify infections and quickly prescribe antibiotics to veterans in rural areas and provide other care that was more safely delivered in private homes.

“The findings from our study highlighted that when working together for the common goal of keeping vulnerable populations like veterans in MFHs [medical foster homes] safe during times of crisis, adaptation and collaboration facilitated the ongoing provision of high-quality care,” Dr. Haverhals’s group wrote. “Such collaboration has been shown to be critical in recent research in the United States on supporting older adults during the pandemic.”

Cari Levy, MD, PhD, a professor at the University of Colorado at Denver, Aurora, and a co-author of the study, specializes in palliative and telenursing home care for the VA.

Dr. Levy, who has worked for the VA for about 20 years, says how medical foster homes provided care during the pandemic carries lessons for civilian clinics. One of the most important lessons, she says, is that medical professionals will need to provide more care where people are, especially in populations that are too sick to get to the clinic.

“For years, there was all this hope that telehealth would expand,” but it took a pandemic to authorize approval from federal agencies to explode, she says. “I shudder to think what would have happened if we didn’t have telehealth. Fortunately, it was the right time to be able to flip a switch.”

Crisis aside, Dr. Levy says her dream would be for health care providers to do more home-based care. The model allows people to preserve the relational aspects of medicine, which can counteract a lot of the moral injury and burnout in the field, she says, adding:

“I see this as the kind of medicine many people intended to do when they got into medicine.”

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

Susan Snead used to live in an apartment complex for older adults. The complex had a nice dayroom, and neighbors would knock on her door every now and then to check in.

But despite not being lonely, Ms. Snead, 89, did live alone in downtown Charleston, S.C. Eventually, that became dangerous.

“I fell a few times,” she says. “I had to call somebody to come and get me up.”

Sometimes help would come from the apartment complex’s office. Sometimes it came with a police escort.

Over time, needing to make those calls became a burden. Making and keeping appointments with her doctor, something she had to do regularly, as she has diabetes, got harder, too.

“It kind of wore me out,” she says. “Like you’re going up a hill.”

As she was beginning to accept she could no longer live alone, Ms. Snead, an Air Force veteran, learned about a program run by the Department of Veterans Affairs called Medical Foster Home.

Medical foster homes are privately owned homes in which a licensed caregiver lives with and supervises residents around the clock. Caregivers help aging veterans with activities of daily living like bathing, cooking, making and getting to appointments, getting dressed, and taking daily medication.

Caregivers can take care of up to three residents in their home at a time. While most residents are veterans, caregivers sometimes care for non-veteran residents, such as a veteran’s spouse or a caregiver’s family member.

Veterans typically pay about $1,500 to $3,000 out-of-pocket per month for the service, depending on location.

According to the VA, the concept of medical foster homes has been around since 1999, when VA hospitals across the country began reaching out to people willing to provide live-in care for veterans. The option is led by local VA hospitals, which approve caregivers and provide administrative services. There are now 517 medical foster homes, the VA says.

Much like other residential care facilities, medical foster homes get regular inspections for safety, nutrition, and more.

In 2019, Ms. Snead signed up for the program. She expected to be cared for, but she found a sense of family with her caregiver, Wilhelmina Brown, and another veteran in the home.

Ms. Brown started taking care of people – but not necessarily veterans – in 1997 when her grandmother was unable to care for herself, she says.

“My grandmama carried me to church every Sunday, she carried me to the beach – everywhere she went, she took me with her,” Ms. Brown says. As her grandmother got older, “I said, ‘I’m going to take care of her in my home.’ ”

Caring for others must come from the heart, Ms. Brown says.

She cooks her residents’ meals three times a day with dietary restrictions in mind, washes their dishes, does their laundry, remembers birthdays, and plans little parties.

“That’s my family,” Ms. Brown says.

In 2020, the COVID-19 pandemic upended the world – but at the same time, it highlighted the advantages of the medical foster home model.

Home-based primary care keeps veterans out of nursing homes – something that became particularly important as COVID-19 hit nursing homes and long-term care facilities.

Caregivers in the system were also able to help veterans, often living in rural areas, pivot and adapt to telehealth during a time of crisis.

One study, published in the journal Geriatrics, set out to identify how medical foster homes were able to deliver safe, effective health care during the early stages of the pandemic.

Researchers interviewed 37 VA care providers at 16 rural medical foster home programs across the country. The interviews took place between December 2020 and February 2021. They found medical foster home caregivers, coordinators, and health care providers communicated to move office visits to the home, helped veterans navigate telehealth, advocated to get veterans vaccinated in-home, and relied on each other to fight social isolation.

Caregivers also adapted quickly to telehealth, according to Leah Haverhals, PhD, a health research scientist and communications director for the Seattle-Denver Center of Innovation for Veteran Centered and Value Driven Care, who led the study.

Most veterans in the foster home program are older and find new technology difficult to use.

Caregivers, coordinators, and health care providers were largely new to the technology, too.

While the study found that most veterans and caregivers preferred in-person care, they were able to work together to make the best of telehealth.

“That speaks to the nature of the care being given, being able to pivot in a crisis like that,” Dr. Haverhals says.

If caregivers didn’t already have computers or telehealth-compatible devices, the VA provided iPads that would connect to the internet using cellular signals. According to the study, this helped to overcome connectivity issues that may have caused problems in rural areas.

Ms. Snead says Ms. Brown helped a lot with her telehealth calls.

“If we had to do things over the phone or with video, she was able to set that up to work with the person on the other end. She knows a lot about that stuff – about computers and things like that,” Ms. Snead says, adding that she hadn’t worked with computers since retirement in 1998.

Telehealth helped health care providers identify infections and quickly prescribe antibiotics to veterans in rural areas and provide other care that was more safely delivered in private homes.

“The findings from our study highlighted that when working together for the common goal of keeping vulnerable populations like veterans in MFHs [medical foster homes] safe during times of crisis, adaptation and collaboration facilitated the ongoing provision of high-quality care,” Dr. Haverhals’s group wrote. “Such collaboration has been shown to be critical in recent research in the United States on supporting older adults during the pandemic.”

Cari Levy, MD, PhD, a professor at the University of Colorado at Denver, Aurora, and a co-author of the study, specializes in palliative and telenursing home care for the VA.

Dr. Levy, who has worked for the VA for about 20 years, says how medical foster homes provided care during the pandemic carries lessons for civilian clinics. One of the most important lessons, she says, is that medical professionals will need to provide more care where people are, especially in populations that are too sick to get to the clinic.

“For years, there was all this hope that telehealth would expand,” but it took a pandemic to authorize approval from federal agencies to explode, she says. “I shudder to think what would have happened if we didn’t have telehealth. Fortunately, it was the right time to be able to flip a switch.”

Crisis aside, Dr. Levy says her dream would be for health care providers to do more home-based care. The model allows people to preserve the relational aspects of medicine, which can counteract a lot of the moral injury and burnout in the field, she says, adding:

“I see this as the kind of medicine many people intended to do when they got into medicine.”

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

A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.