I asked Gemini why NSAIDs (Loxonin) cause lower gastrointestinal bleeding
Lower gastrointestinal bleeding after a barium test.
I thought maybe the barium hardened and caused a tear without me noticing, but that wasn't it. The culprit this time was the laxative used to flush out the barium.
Actually, I've had severe lower GI bleeding several times, and as a countermeasure, I've been taking Biofermin and Bios-3 daily. With this latest episode, the sequence of events has become clear, so I can take action. This time, it was:
Laxative → Loxonin → Lower GI bleeding
Before, it was:
Antibiotic → Loxonin → Lower GI bleeding
Mountain wasabi ramen → Loxonin → Lower GI bleeding
In short,
It seems that if I take Loxonin while my gut microbiota has been washed out, I will definitely experience lower GI bleeding.
I asked Gemini's thinking mode what this was all about, and the solution became clear.
Solution: Stop taking Loxonin and get a prescription for Celecoxib!
There's no way I could have figured this out on my own no matter how much I researched. Thank you, AI.
If you are taking regular medication, mountain wasabi ramen can be dangerous, so it's best to avoid it.
Below is Gemini's response
Why do NSAIDs (non-steroidal anti-inflammatory drugs), including Loxonin (loxoprofen), cause ulcers in the large intestine? The mechanism is explained by a complex process medically known as the **"Multi-hit hypothesis."**
It is not simply because "stomach medicine doesn't work there." It is a combination of sabotage at the cellular level and unfortunate anatomical factors.
I will explain the professional mechanism in three stages.
Stage 1: Direct attack on cells (topical effect)
This is damage caused by Loxonin coming into direct contact with intestinal mucosal cells.
Mitochondrial dysfunction:
When NSAID components enter intestinal epithelial cells, they damage the mitochondria, the cell's energy factories. Specifically, they cause a phenomenon called "uncoupling of oxidative phosphorylation," preventing the cells from producing the energy (ATP) they need to survive.Destruction of intercellular junctions:
Cells that become energy-deficient can no longer maintain the junctions (tight junctions) that hold them together. This destroys the intestinal barrier function, causing gaps to open between cells (increased permeability).
【The Loxonin Trap】
Loxonin is a "prodrug" (a drug that becomes active only after being metabolized in the body) to reduce the burden on the stomach. It passes through the stomach, but after being activated in the liver, the components not only enter the bloodstream but are also excreted into the small and large intestines via **bile**. In other words, highly active components are poured directly onto the mucosa of the large intestine.
Stage 2: Reduced defense capability (systemic effect)
Damage caused by systemic effects of components absorbed into the bloodstream.
Inhibition of COX (cyclooxygenase):
This is the primary action of painkillers, but it also stops the production of **prostaglandins (PG)**, which protect the mucosa.Reduced blood flow and mucus depletion:
When PG levels drop, blood flow to the intestinal mucosa decreases (ischemia), and the secretion of protective mucus also decreases. As a result, the intestinal wall is left with almost zero defense.
Stage 3: Gut bacteria and enterohepatic circulation (the finishing blow)
This is the point unique to the large intestine, and the most troublesome one.
Recycling damage from enterohepatic circulation:
Once absorbed, Loxonin components are returned to the intestine from the liver as bile. They are reabsorbed in the intestine and return to the liver... this cycle repeats. As a result, the mucosa of the large intestine is exposed to high concentrations of the drug for a long period.Invasion of gut bacteria:
Through the gaps in the mucosa where the barrier was destroyed in stages 1 and 2, **gut bacteria and toxins (such as LPS)**, which are abundant in the large intestine, invade deep into the mucosa.Excessive inflammatory response:
White blood cells (neutrophils) gather to attack invading bacteria, causing an intense inflammatory response. This destroys tissue and forms deep ulcers.
Summary: Why it is fatal for UC patients
Even in healthy people, this process creates "NSAID ulcers," but for patients with ulcerative colitis (UC), the risk skyrockets for the following reasons.The barrier is already weak: Since the mucosal barrier is already weakened in UC, it is easier for the first stage of damage to occur.
Hypersensitive immune system: When bacteria invade (the third stage), the inflammatory response is more likely to become intense and run out of control compared to healthy individuals.
In other words, Loxonin creates the worst possible environment for the large intestine by "breaking the barrier (direct action), cutting off supply lines (reduced blood flow), and inviting in the enemy (bacteria)."
What if I switch from Loxonin to Celecoxib?
To give you the conclusion first, with Celecoxib (Celecox), the "Stage 1: Direct attack on cells (topical effect)" explained for Loxonin is generally considered not to occur (or to be extremely weak).
This is one of the biggest reasons why Celecoxib is said to be "gentle on the stomach and intestines."
I will explain the difference between why it happens with Loxonin and not with Celecoxib.
🙅♂️ Why can Celecoxib avoid the "first stage"?
The reason lies in the difference in the chemical "acidic/alkaline" properties of the drugs.
Conventional NSAIDs like Loxonin (acidic)
Properties: Many NSAIDs are "acidic" drugs.
Occurrence of the first stage: When acidic drugs pass through intestinal cell membranes and enter the cells, they cause a phenomenon called "ion trapping" inside the cells. They become trapped inside the cell at high concentrations, where they directly attack and destroy mitochondria. This is the true nature of the first stage.
Celecoxib (non-acidic)
Properties: Celecoxib has a "non-acidic (neutral/weakly basic)" chemical structure.
Avoidance of the first stage: Because it is not acidic, even if it enters the cell, it has almost no effect of attacking mitochondria or interfering with energy production (uncoupling of oxidative phosphorylation).
Result: Since its power to directly damage intestinal cells themselves is very weak, the destruction of intercellular junctions (decline in barrier function) is also less likely to occur.
⚠️ However, why is it a "caution" for UC patients?
You might think, "If there is no 'first stage' (direct attack), isn't it safe?"
However, there is another reason why it is still used cautiously for patients with ulcerative colitis (UC).
Weakening the "power to heal wounds"
Although not as much as Loxonin, the second stage of "COX (cyclooxygenase) inhibition" is also related to Celecoxib.
Role of COX-2: In fact, the enzyme COX-2, which causes inflammation, is also a necessary enzyme for repairing and healing existing ulcers.
Risk: UC patients often already have small wounds or inflammation in their intestines. If Celecoxib strongly suppresses COX-2, there is a risk that it will "not create new wounds, but slow down the healing of existing ones."
Allergies and individual differences
Although rare, colitis can worsen due to allergies to the components of Celecoxib (sulfonamide group) or if it does not suit the individual's constitution.
Summary
Loxonin: Has a strong power to bomb mitochondria and "destroy the barrier (first stage)."
Celecoxib: Has almost no power to destroy the barrier (first stage).
Therefore, if a painkiller is absolutely necessary, Celecoxib causes significantly less damage to the large intestine than Loxonin, both theoretically and clinically.