Heartburn and Dementia

Yet another class of drugs with unexpected side effects. Here we go again!

Here’s the situation:

  1. Excess acid in the body contributes to a number of conditions, including heartburn, gastritis and stomach ulcers. Acidic hydrogen atoms are produced in the mucosa (tissue that lines caveties in the body such as the nose and mouth as well as covers some organs — think mucus).
  2. Drugs called proton pump inhibitors (PPIs) reduce the volume of these hydrogen atoms, reducing this excess acidity and the damage it causes. Examples of PPIs include Prilosec, Zantac, Prevacid and Nexium.
  3. Prior statistical studies had shown a higher incidence of dementia among longterm users of these drugs, but provided no explanation for that.
How PPIs work Source: Slideshare

Researchers at the Karolinska Institutet in Sweden have now given us insight into the rest of the story.

  1. If the impact of PPIs stopped with the reduction in hydrogen ions, all would be well and good. However, that’s not the case.
  2. PPIs interact with another substance, choline acetyletransferase, the purpose of which is to synthesize (create) and neurotransmitter, acetylcholine. The acetylcholine is required to transmit nerve signals between cells, but only works when it is present in a sufficient quantity. PPIs effectively reduce the production of acetylcholine.
  3. And that brings us to a functional definition of dementia — the failure of messages to travel between brain cells.

As I’ve argued in prior posts, a statistical finding can’t really be considered a “fact” until there is an understanding of the mechanics underlying that finding. A lot of people didn’t accept the idea that cigarettes could cause cancer until we understood the mechanism by which that occurs. Data without the mechanical explanation is why apparently conflicting articles about diets drive so many people nuts.

However, once the mechanism is identified, a finding moves from “hypothesis” to “fact” status. The relationship between PPI use and dementia has just crossed that line.

PPIs may be essential for some people, but the Swedish team cautions that they should be used only as needed.

“Since there’s no effective treatment for the disease [dementia], it’s important to avoid risk factors. We therefore want to draw attention to this so that the drugs [PPIs] aren’t used needlessly for a long time.”(2)

Sources:

  1. Rajnish Kumar, Amit Kumar, Agneta Nordberg, Bengt Långström and Taher Darreh-Shori. Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme – A plausible missing link for their association with incidence of dementia. Alzheimer’s & Dementia, May 8, 2020 DOI: 10.1002/alz.12113
  2. Karolinska Institutet. “Newly discovered mechanism can explain increased risk of dementia.” ScienceDaily. ScienceDaily, 8 May 2020. <www.sciencedaily.com/releases/2020/05/200508083549.htm>.

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