• Researchers investigated the effects of laxatives on dementia risk.
• They found that regular consumption of laxatives increases dementia risk.
• They noted that further studies are needed to confirm their findings.

Around 20% of the general population, 40% of community-dwelling older adults, and 70% of nursing home residents live with constipation.

In the United Kingdom, around 85% of people with constipation are treated with laxatives. As laxatives are available over the counter, laxative abuse is common in middle-aged and older adults.

Studies show that laxative use can influence gut microbiota composition and induce long-term changes in the immune response. Research also shows that these changes may increase the production of toxins linked to inflammation, neural damage, and amyloid deposition- a biomarker for dementia.

Further investigation of how using laxatives and other agents that disrupt the microbiome may affect dementia could lead to improved treatment and prevention strategies.

Recently, researchers analyzed healthcare data to see whether laxative use is linked with dementia onset. They found that regular use of laxatives is linked to a higher risk of all-cause dementia.

“This study reports individuals with more laxative use have an increased likelihood of developing dementia relative to those with less laxative use,” Russell Swerdlow, neurologist, and co-director of KU Alzheimer’s Disease Research Center, not involved in the study, told Medical News Today.

“It is interesting that people with at least one dementia-associated illness, Parkinson’s disease, experience constipation at a higher frequency than those without Parkinson’s disease,” he pointed out.

“[P]erhaps there are those who will now want to study how laxatives may cause dementia, although at least on a superficial level, it would seem to make more sense to study how the biology that underlie dementia may impact the gastrointestinal tract,” he added.

The study was published in Neurology.

Up to 65% increased risk

The researchers analyzed healthcare data from 502,229 participants with an average age of 56.5 years from the U.K. Biobank.

Altogether, 54.4% were female, and 3.6% reported regular laxative use (self-reported) on most days of the week for the last four weeks.

Over an average follow-up time of 9.8 years, 1.3% of participants who used laxatives and 0.4% of non-users developed dementia.

After adjusting for demographic factors, they found that laxative use increased all-cause dementia risk and vascular dementia risk by 51% and 65%.

They further found that dementia risk increased alongside the number of regularly used laxative types. All-cause dementia risk increased by 28% for those using a single laxative type and 90% for those using two or more laxatives compared to non-users.

No increased risk for Alzheimer’s

The researchers noted, however, that laxative use was not linked to an increased risk for Alzheimer’s, comprising 60-70% of dementia cases.

“The findings of this study suggested that regular use of laxatives, even without short-term severe adverse events, may have the potential long-term risk of dementia, especially when it comes to osmotic laxatives and combination use of two or more types of laxatives,” Feng Sha, associate professor at Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, one of the corresponding authors of the study, told MNT.

“In fact, osmotic and stimulant laxatives are both not recommended for regular use, yet we still found many regular users of these medications in this study,” he noted.

Osmotic laxatives work by drawing water into the stool to soften it so it may pass more frequently. Stimulant laxatives work by encouraging muscle contractions that move along the stool mass.

Is a disrupted microbiome to blame?

“While the exact mechanisms linking laxatives with dementia have yet to be investigated, one possible explanation is that laxatives can influence gut microbiome composition and cognitive function in the microbiome-gut-brain axis,” noted Prof Sha.

“The alteration of gut microbiota may affect the production of numerous neurotransmitters for normal cognitive function and increase the production of intestinal toxins that are associated with the inflammatory response. Laxatives may also disrupt intestinal epithelial barrier (the intestinal lining) and facilitate passage of gut microbial-derived neurotoxic metabolites into the central nervous system.”
— Feng Sha, study author

He continued that some microorganisms may then reach the brain in conditions with reduced barrier function, such as stroke—a known risk factor for dementia.

“Indeed, gut bacteria [imbalance] caused by laxatives could increase production of trimethylamine N-oxide (TMAO)—a gut-derived metabolite—and its entry to the blood. High plasma TMAO levels lead to platelet hyperactivity, thrombosis, vascular inflammation, and atherosclerosis that contribute to the pathology of stroke and vascular dementia,” he elaborated.

No causal link, yet

“The study shows a correlation in its findings but not necessarily causation, as it points out a 51% increase in the risk of dementia compared to those who do not use laxatives, with a test group of about 500,000 that used laxatives,” psychiatrist Dr. Howard Pratt, behavioral health medical director at Community Health of South Florida, Inc. (CHI), who was not involved in the study, told MNT.

“So, that’s not to say that people who use laxatives are going to get dementia, but that the study is pointing out a correlation,” he noted.

Prof Sha added that they were not able to take into account personal factors that predispose laxative use, such as dietary fiber intake and severity of constipation, and that they did not explore the dose-response relationship between laxative use and dementia risk.

Should I stop using laxatives?

“While 500,000 is a significant number of people looked at in the study, this is something that needs to be explored further,” said Dr. Pratt.

“This is not to say that people should stop using laxatives altogether; however, they should also focus on a high fiber diet and increased water intake because a lot of these laxatives can dehydrate a person, and dehydration is one of the most common causes of constipation.”
— Dr. Howard Pratt

“Many constipation patients may misuse laxatives because they tend to self-treat with the OTC medications. Therefore, pharmacists and clinicians should be well-placed in providing instructions for patients regarding the use of OTC medications for treating constipation,” Prof Sha cautioned.

Dr. Sha added that further studies are needed to confirm the link between laxative use and dementia.

“More studies are also needed to identify potential contributory factors or specific mechanisms that may be responsible for the observed associations in our study,” he said.

“[Future] studies should also investigate its associations with other chronic diseases, such as stroke, depression, and Parkinson’s diseases that may be linked through the same mechanisms,” he added.

“Instead of regular use of laxatives, constipation can be mitigated most of the time by lifestyle changes, such as increasing fluid intake, dietary fiber, and activity levels, which may also benefit brain health.”
— Feng Sha

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