NSAIDs Cause Leaky Gut and New Allergies (With Natural Alternatives)

The Pharmaceutical Industry “Gateway” Drug

Just because something is sold over the counter doesn’t make it safe.

Especially with non-steroidal anti-inflammatory drugs (NSAIDs), which can cause autoimmune diseases and destroy cells.

This post will provide alternatives and a safer way to taking NSAIDs.




  1. Basics
  2. Downsides Of NSAIDs
  3. Alternatives To NSAIDs
  4. If You Must Go On A NSAID
  5. Mechanism Of Action
  6. More Research


Non-steroidal anti-inflammatory drugs (NSAIDs) are also known as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) and nonsteroidal anti-inflammatory medicines (NSAIMs).

They are very commonly used for acute injuries and autoimmune disorders (like rheumatoid arthritis). R 

Common names include ibuprofen (Advil and Motrin) and aspirin (see more below). R

They have been used for a long time in the industry and do have some benefits:

  • Controls Pain (including Biliary Colic) R
  • Protects Against Cancers R R R R
  • Protects Against Alzheimer’s Disease R R
  • Protects Against Parkinson’s Disease (possibly) R
  • Reduces Fever R

But the problems they cause can severely outweigh the benefits, as they do not fix the underlying cause. R

NSAIDs are like the “gateway” drug of the pharmaceutical companies (it will become clear why below).

The damage NSAIDs cause to the body (as described below in the downsides section) create a negative feedback loop.

This means by taking NSAIDS, you can damage the organ systems, creating more inflammation, and creating the need to take stronger and more NSAIDs or even immunosuppressants, contributing to further inflammation and damage.  

Big pharma knows about these dangers and continues to push them anyway.

Downsides Of NSAIDs

1. Damage Mitochondria



Mitochondria are little bacteria that live inside our cells to create usable energy (ATP). R

In the mitochondria, NSAIDs are competitors to ATP synthase (the enzyme that creates ATP), meaning they directly inhibit the production of energy. R

Also, NSAIDs induce mitosis (programmed mitochondrial death). R  

One way they do this is by creating reactive oxygen species (ROS, which are damaging free radicals). R

This causes oxidative stress in the cells and the body and depletes the body of its natural antioxidants, such as glutathione. R R

This abundance of oxidative stress ends up leading to cell death, which is seen in most chronic illnesses. R

2. Damage The Vascular System

NSAIDs increase the risk of developing a heart attack by 10-fold. R R

One reason for this is that the heart and arteries become damaged from ROS that NSAIDs produce. R

There is also less ATP, which is the energy your heart needs to keep pumping. R

NSAIDs cause an increase of NADPH oxidase, which is a major cause of atherosclerosis (hardening of the arteries) and autoimmune diseases. R R R

NSAIDs also cause high blood pressure. R

This is because they inhibit nitric oxide’s (NO) ability to relax the arteries. R

NSAIDs lower tetrahydrobiopterin (BH4 – an important enzyme that protects against heart disease and helps produce key neurotransmitters). R

NSAIDs use is also correlated with developing atrial fibrillation (irregular heartbeats). R R

Erection problems are a good sign of vascular dysfunction. R

Use of NSAIDs have been linked with erectile dysfunction. R

3. Damage The Brain

NSAIDs easily cross the blood-brain barrier (BBB). R

NSAIDs increase the risk of having a stroke (increases the risk of ischemic more than hemorrhagic). R

This is because NSAIDs inhibit the synthesis of platelet formation, which is necessary to form blood clots. R

NSAIDs have also shown to cause meningitis (inflammation of the brain). R

High doses of NSAIDs may cause epilepsy and seizures, while low doses may prevent it. R R

4. Damage The Gut



The most common (40–90% of NSAID users) symptoms seen with NSAIDs are dyspepsia (indigestion) and intestinal bleeding (from gut damage and peptic ulcers). R R

This is because NSAIDS damage the gut lining, causing intestinal permeability (aka leaky gut, especially in the small intestine). R

Damage to the gut allows other inflammatory molecules (like bacteria, inflammatory fats, and food proteins) to pass through the gut lining, and thus causing more inflammation to the body. R

Bile acids (naturally produced from the liver) cause further damage to the intestinal lining from NSAIDs. R 

NSAIDs synergize with H. Pylori to form ulcers. R

This is why Irritable Bowel Syndrome (IBS – stomach pain including diarrhea and constipation) is so common with NSAID use. R

There is also a correlation between NSAID use and Small Intestinal Bacterial Overgrowth (SIBO – where bacteria from the colon move up to the small intestine). R

NSAIDs change the composition of the gut microbiome, decrease the healthy diversity of the gut biome and cause dysbiosis. R R

NSAIDs can also cause intestinal webbing (which is webbing of the insides of the intestines causing bowel obstruction).  R

They also increase the chance of developing colon and rectal cancers. R

NSAIDs are commonly prescribed with proton pump inhibitors (PPIs), which have their own downsides to creating leaky gut and mitochondrial damage. R R

5. Damage The Kidneys

Chronic Kidney Disease (CKD) and Acute Kidney Failure (AKF) is common with NSAID use. R R R

This is because NSAIDs damage the kidneys, increase salt retention in the body, and decrease the body’s supply of potassium. R

NSAIDs also contribute to:

  • Acute Tubular Necrosis R
  • Interstitial Nephritis R
  • Nephrotic Syndrome R
  • Renal Papillary Necrosis R

Taking ACE inhibitors, phenacetin, or acetaminophen further increases the chances of developing kidney issues. R R

6. Damage The Liver

Several NSAIDs have been withdrawn from the market due to hepatotoxicity (damage to the liver). R

NSAIDs block farnesoid X receptor (FXR – which helps regulate cholesterol levels). R R

FXR also suppresses inflammation of the liver. R

Blocking FXR increases the risk of developing non-alcoholic fatty liver disease (NAFLD), and cirrhosis (scarring of the liver). R R

NSAIDs also increase the risk of developing Reye’s Syndrome (toxicity to the liver accompanied by neurological problems and death). R R

7. Damage The Ears



NSAIDs can cause tinnitus. R

This happens because excessive ROS will accumulate in the cochlea. R

Also, NSAIDs cause reduced cochlear movement, which is necessary for protection of cochlear hair health. R

Long term use may contribute to hearing loss.  R

8. Decrease Bone Density

NSAIDs decrease bone density. R

They increase the risk of osteoporosis and bone fractures. R

They also stop bones from healing and repairing themselves. R

9. Cause Birth Defects

NSAIDs can cause premature birth and kidney failure to the fetus. R R R R

This effect is more pronounced especially in the third trimester of pregnancy. R

Most people will turn to acetaminophen (Tylenol), but that can make male children infertile and born with liver damage. R R R

10. Induce New Allergies

NSAIDs can cause hypersensitivity to allergies. R

NSAIDs increase the chances of creating new allergies as well. R

They degranulate mast cells (contributing to brain fog, but in this instance is unrelated to histamine intolerance). R 

Mastocytosis makes this worse. R

NSAIDs cause increased photosensitivity (sensitivity from exposure to sunlight). R

They also increase the risk of developing a photoallergic reaction to the sun. R

11. Change Hormones

In humans, NSAIDs can lower cortisol. R

They can also increase testosterone. R

Alternatives To NSAIDs



Most of these will inhibit the COX-1 or COX-2 pathway, or has some benefit related to inflammation-based pain. 




  • Ketosis R
  • Meditation R
  • Physical Therapy
  • Sauna R
  • Sun Exposure P R
  • Vagus Nerve Stimulation (use code LHE to get 15% off) R
  • Yoga (breathing techniques in Yoga are important for the anti-inflammatory effect) R
  • Pathways

    • Activate AMPK R
    • Activate Endocannibinoids (take CBDTHC works, but can cause memory impairment) R R R R
    • Activate PPARgamma R
    • Activate NRF2 R
    • Increasing BDNF R
    • Inhibit FAAH R
    • Inhibit GSK-3 R
    • Inhibit HO-1 R
    • Inhibit TRPV1 R


    What To Avoid

    • Alcohol R
    • Arachidonic Acid R
    • Casein (A1 is bad, A2 is fine) R
    • Exercise R
    • Gluten R
    • Lectins R
    • Mold R
    • Omega 6’s R

    If You Must Go On A NSAID

    Protect Your Body

    Taking BPC-157 would be a good idea, as it can heal and counteract the damage in the gut and brain. R

    Colchicine would help the small intestine as well. R

    Taking CoQ10, quercetin, and glutathione would help protect against mitochondrial damage. R R

    Inhibiting GSK3β (with luteolin or apigenin) would decrease damage to the kidneys. R R

    Taking potassium would help with some of the electrolyte imbalances. R

    Taking fish oil would help against liver damage. R


    • ACE Inhibitors R
    • Blood Thinners R
    • Glucocorticoids (exacerbate the damage done by NSAIDs) R
    • Lithium R
    • Methotraxate R
    • Other COX-2 Inhibitors R
    • Proton Pump Inhibitors R
    • SSRI Antidepressants R

    Mechanism Of Action





    • NSAIDs are metabolized in the liver and their inactive metabolites that typically are excreted in the urine.
    • Some other metabolites are partially excreted in bile via the liver.
    • Their half-lives can vary from 2-3 hours (like ibuprofen) to 20-60 hours (like oxicams). 


    • NSAIDs inhibit the activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby the synthesis of prostaglandins and thromboxanes.
    • Normally COX produces prostaglandins, most of which are pro-inflammatory, and thromboxanes, which promote clotting.
    • This inhibition is competitively reversible, except with Aspirin, which irreversibly inhibits COX1. 
    • COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2).
    • Prostaglandins act (among other things) as messenger molecules in the process of inflammation.
    • COX-1 is a constitutively expressed enzyme with a “house-keeping” role in regulating many normal physiological processes.
    • One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid.
    • COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.
    • COX1/COX2 inhibitors lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result.
    • Acetaminophen blocks COX2 in the CNS, but not the rest of the body. R
    • NSAIDs inhibit urate crystal phagocytosis. R
    • NSAIDS have antipyretic (antifever) activity and can be used to treat fever. R R
    • Fever is caused by elevated levels of prostaglandin E2, which alters the firing rate of neurons within the hypothalamus that control thermoregulation. R R
    • Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus. R R
    • PGE2 signals to the hypothalamus to increase the body’s thermal set point. R R
    • Aspirin enhances Ca2+ influx, while at high concentrations, it suppresses Ca2+ influx. R
    • Permeability across the small bowel mucosa increases, facilitating invasion of small bowel by luminal injury factors such as enterobacteria and bile. R
    • Gram-negative bacteria having invaded the small bowel mucosa activate toll-like receptor 4, a receptor for lipopolysaccharide, and induce excessive expression of cytokines such as tumor necrosis factor-α through activation of the transcription factors nuclear factor kappa B, leading to neutrophil infiltration. R
    • NSAIDs (and bile) open up mitochondrial permeability transition pore (PTP) allowing cyctochrome c release. R
    • NSAIDs increase potassium release and decrease eGFR. R
    • NSAIDs protect dopamine neurons against glutamate induced excitotoxicity. R
    • But salicylate induced tinnitus happens through the activation of these cochlear NMDA receptors. R
    • Some NSAIDs raise inflammatory markers (IL-8, MCP-1, and TNFα). R

    Other NSAIDs include:

    • Aceclofenac
    • Aspirin (acetylsalicylic acid)
    • Celecoxib (FDA alert)
    • Clonixin
    • Dexibuprofen
    • Dexketoprofen
    • Diclofenac
    • Diflunisal (Dolobid)
    • Droxicam
    • Etodolac
    • Etoricoxib not FDA approved, licensed in the EU
    • Fenoprofen
    • Firocoxib
    • Flufenamic acid
    • Flurbiprofen
    • Ibuprofen
    • Indomethac
    • Isoxicam (withdrawn from market 1985)
    • Ketoprofen
    • Ketorolac
    • Licofelone acts by inhibiting LOX (lipooxygenase) & COX and hence known as 5-LOX/COX inhibitor
    • Lornoxicam
    • Loxoprofen
    • Lumiracoxib TGA cancelled registration
    • Meclofenamic acid
    • Mefenamic acid
    • Meloxicam
    • Nabumetone
    • Naproxen
    • Nimesulide (systemic preparations are banned by several countries for the potential risk of hepatotoxicity)
    • Oxaprozin
    • Parecoxib FDA withdrawn, licensed in the EU
    • Phenylbutazone (Bute)
    • Piroxicam
    • Rofecoxib (withdrawn from market)
    • Salicylic acid and other salicylates
    • Salsalate (Disalcid)
    • Sulindac
    • Tolfenamic acid
    • Tolmetin
    • Tenoxicam
    • Valdecoxib (withdrawn from market)

    More Research

    • Origins and impact of the term ‘NSAID’ R
    • Testosterone induces leucocyte migration via NADPHox- and COX2-dependent mechanisms and may contribute to inflammatory processes and oxidative stress in the vasculature potentially increasing cardiovascular risk. R