New study links many popular OTC drugs to Alzheimer’s disease

This article was previously published on August 1, 2019 and has been updated with new information.

According to statistics for 20191, 14% of Americans aged 71 or older have some form of dementia. Alzheimer’s disease, the most serious and deadly form of dementia, affects an estimated 5.8 million Americans. Of these, 81% are older than 75 years, but about 200,000 are younger than 65 years. Overall, 1 in 10 seniors over the age of 65 have Alzheimer’s disease.

Due to the high prevalence of dementia and the scarcity of effective conventional treatments, prevention is paramount. I’ve written many articles on the subject, focusing on some of the most important prevention strategies, including dietary recommendations and the need for exercise, sun exposure, and avoidance of toxins.

One risk factor that has received much less attention is drug side effects, which we will focus on here. One class of drugs that have been shown to be of great concern in this regard are anticholinergics — drugs that block acetylcholine, a neurotransmitter that performs important functions in your brain and peripheral and central nervous systems.

In your nervous system, it acts as both an activator and an inhibitor,2 which is partly why it’s used in such a wide variety of medications. Acetylcholine, for example, causes muscle contractions and pain responses and is involved in the regulation of your endocrine system and the REM sleep cycle.

In your brain, it is a major player in attention, concentration,3,4 memory formation and consolidation,5 which is exactly why these drugs can cause symptoms identical to dementia.

Acetylcholine Blockers May Cause Dementia Symptoms

Anticholinergics are prescribed for a wide variety of conditions, including depression, incontinence, diarrhea, dizziness, motion sickness, insomnia, allergies, and epilepsy.6,7 You can find a long list of anticholinergics and the various conditions for which they are used at 8 As reported in a July 2019 article on

“In all respects, the woman, in her late 60s, appeared to have severe dementia. She was largely incoherent. Her short-term memory was terrible. She was unable to focus on questions that medical professionals were asking her.

But Dr. Malaz Boustani, a professor of aging research at Indiana University School of Medicine, suspected something else might be going on. The patient took Benadryl for seasonal allergies, another antihistamine for itching, Seroquel (an antipsychotic) for mood swings, as well as medications for urinary incontinence and gastrointestinal upset.

Each of these drugs blocks an important chemical messenger in the brain, acetylcholine, to varying degrees. Boustani thought the cumulative impact could cause the woman’s cognitive problems. He was right.”

When the patient was taken off these drugs over a six-month period, she recovered what appeared to be a “miraculous” recovery; her scores on the mini-mental state exam went from indicative of severe dementia back to normal.

Research Points to Risks of Anticholinergics

A June 201910 study in JAMA that assessed the risk of dementia associated with several anticholinergics found that the link was strongest for:

Antidepressants (tricyclic antidepressants such as imipramine,11 doxepine or amitriptyline have strong anticholinergic effects, while SSRIs such as citalopram and duloxetine have less anticholinergic effects12) Anti-Parkinson drugs Antipsychotics (such as clozapine,13 chlorpromazine or olanzapine14) Anti-depressant drugs,15 prescribed for overactive bladder (such as oxcarbazepine or carbamazepine16)

A case-control study17, published in 2018 in the BMJ, which, like the JAMA study just mentioned, looked at the effects of different classes of anticholinergics, also found that antidepressants, urologic and anti-Parkinson drugs posed the greatest risk.

Similarly, a previous study,18 published in JAMA Internal Medicine in 2015, found that “Higher cumulative use of anticholinergics is associated with an increased risk of dementia,” including Alzheimer’s disease, and that use of anticholinergics should be minimized to prevent this. drug-related risk.

Overall, high use of anticholinergics for three years or more was associated with a 54% increased risk of dementia, compared with non-use.19 In addition, they concluded that this increased risk persisted even after the drug or drugs were discontinued. .

According to KHN20, a new study will investigate this further, to see whether patients taking anticholinergics and whose cognition has already begun can restore their brain function, or whether the effects of the drugs have a more lasting effect.

Many nonprescription drugs have anticholinergic effects

Importantly, anticholinergics are not prescription-only. Many common over-the-counter medications also contain anticholinergic ingredients. These include21 antihistamines sold under the brand names Benadryl and Chlor-Trimeton, sleep aids such as Tylenol PM, Aleve PM and Unisom, the motion sickness medication Dramamine and various cold remedies.22

In the case of Benadryl and many sleep aids, the anticholinergic ingredient in question is diphenhydramine. In Chlor-Trimeton it is chlorpheniramine; in many cold medicines it is pyrilamine

Because there are so many different drug ingredients with anticholinergic effects, it can be quite difficult to identify them, making concomitant use of more than one anticholinergic in many cases likely. The end result can be severe, dementia-like symptoms, such as those experienced by Boustani’s patient.

So, for your own safety, take the time to research any medications you take regularly or even semi-regularly, including OTC drugs, to identify the drugs with anticholinergic effects. Don’t assume that your doctor will keep track of this or warn you about the dangers of anticholinergics. As noted by KHN:24

“Physicians often attribute anticholinergic symptoms in the elderly to aging or age-related diseases rather than to the effects of drugs,” according to a research review25 by physicians from the Medical University of South Carolina and in the UK.

Unfortunately, drug side effects are rarely the first suspect when new disease symptoms appear, which is why it’s so important to do your research and know about the potential side effects.

A list of anticholinergic ingredients used in antihistamines, Parkinson’s drugs, muscle relaxants, antiarrhythmics, antidepressants, antimuscarinics for urinary incontinence, antipsychotics, antispasmodic drugs, and antiemetics can be found at the bottom of the “Anticholinergic Drugs to Avoid in the Elderly” page. 26

Importance of choline for dementia prevention

Choline27 is a precursor to acetylcholine and is an essential nutrient not only for your brain and nervous system, but also for your cardiovascular function. The Institute of Medicine officially recognized choline as an essential nutrient for human health in 1998

Aided by a transport protein, choline combines with acetyl coenzyme A at the neuron terminal to form the neurotransmitter acetylcholine. Sufficient amounts of choline must be available in your brain at all times for your neurons to function properly.29 Choline has also been shown to protect against Alzheimer’s disease.

Lowering your homocysteine ​​levels, an amino acid that has been shown to cause neurodegeneration and is involved in the formation of amyloid plaques, two hallmarks of Alzheimer’s disease. Choline converts homocysteine ​​to methionine, which has a number of beneficial effects. Inhibiting microglia activation. Microglia cells clear debris from your brain, and while this is a crucial function, in Alzheimer’s disease the microglia tend to become overactive, causing inflammation in the brain that can lead to neuron death. By reducing the activation of microglia, choline may help protect Alzheimer’s patients from further brain damage.

Other Health Benefits of Choline

Choline is also involved in the synthesis of phospholipids necessary for healthy cell structures. The most abundant phospholipid is phosphatidylcholine, better known as lecithin, which makes up between 40% and 50% of your cell membranes.31 Choline is also needed for:32

Mitochondrial function – A 2014 study33 found that choline is important for healthy mitochondrial membranes in liver cells, and an animal study34 published in 2010 also reported that choline-deficient diets impaired cognition and motor coordination by causing mitochondrial dysfunction in the brain . As noted by the authors, their findings “underscore that, like the liver, the brain also needs enough choline to function normally.” Healthy fetal development35 — Choline is required for proper neural tube closure36, brain development and healthy vision.37 Research shows that mothers who get enough choline give their child a lifelong improvement in memory due to changes in hippocampal development (memory center) of the child’s brain.38 Epigenetic regulation of gene expression – As explained in a 2013 paper39 “The intake of methyl donors such as choline affects the methylation of DNA and histones, altering the epigenetic regulation of gene expression.” Fat Transport and Metabolism – Choline is needed to transport cholesterol from your liver; choline deficiency can lead to excessive fat and cholesterol buildup, resulting in fatty liver

Studies have linked higher choline intake to a range of benefits, including a reduced risk of death from heart disease,42 a 24% lower risk of breast cancer43 and the prevention of non-alcoholic fatty liver disease (NAFLD).44,45,46

In fact, choline appears to be an important controlling factor in the development of fatty liver, as it promotes the secretion of very low-density lipoprotein (VLDL) particles in your liver, which in turn are needed to safely transport fat from your liver.47 Research has also found evidence for choline’s epigenetic mechanisms,48 which also helps explain how choline helps maintain healthy liver function.

Are you getting enough choline to protect your health?

Although a dietary reference value has not yet been established for choline, the Institute of Medicine has established an “adequate daily intake” value of 550 milligrams per day for adult men and 425 mg for adult women49 for the prevention of liver damage.

However, keep in mind that requirements can vary greatly depending on your overall diet, age, ethnicity50 and genetic makeup.51 Pregnant and breastfeeding women, athletes and postmenopausal women typically require higher amounts and diets high in (incidentally) healthy) saturated fats can also increase your need for choline

The tolerable upper intake level for choline is 3.5 grams per day. Side effects of excessive choline include low blood pressure, sweating, diarrhea, and a fishy body odor

Eggs are a primary source of dietary choline; with 115 mg of choline per egg yolk54 they are an easy way to ensure adequate. Other healthy sources of choline55 include organic grass-fed beef, organ meats (kidney and liver), organic chicken or turkey. Supplementation, also with krill oil, is another option if you’re concerned about getting enough choline from your diet.

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