Theophylline: My Most Effective "Shortness of Breath" Treatment
If you're reading this, I'm assuming you're struggling with persistent shortness of breath and have already exhausted the standard treatments: ICS inhalers, albuterol, LAMA inhalers, montelukast, and possibly even expensive biologics like Xolair or Tezspire.
These are invariably the first interventions any pulmonologist will prescribe. And if you're like me (or most long COVID patients), they've delivered disappointing results.
You see - I'm not interested in re-discussing those conventional approaches we've all likely already tried.
What interests me are the overlooked options. Drugs with compelling biochemical rationales that most physicians have forgotten or never learned to use in the first place.
Meet theophylline: a medication synthesized in 1888 that may help shortness-of-breath sufferes, when everything else fails.
The Possible Problem: Corticosteroid Resistance in Long COVID
During the last few years of researching long-covid biochemistry and pharmacology in an effort to solve my Long Covid case, I obviously learned about all the basics (beta-agonists, corticosteroids, leukotriene inhibitors, and biologics).
Unfortunately, none of these options tackle corticosteroid resistance (aka steriod-resistant lung inflammation). Which I believe is one of the core reasons none of these standard options ever worked for me.
After 12 months battling breathing problems that left six pulmonologists with zero answers — each insisting my inhalers should be working. I started looking into potential reasons why my respiratory cells were refusing to respond to them.
My Experiment
For 12 months, I was a walking case-study for "treatment-resistant dyspnea", despite my normal pulmonary function tests.
I experienced the following:
Maximum walking distance: 200 meters before air hunger
VO2 max: 40% below average for my age-group
Constant "air hunger" 24/7
& I tried everything:
High-dose inhaled corticosteroids (Trelegy, Symbicort)
Bronchodilators (Ventolin)
Montelukast for leukotriene pathway modulation
Two monoclonal antibody treatments costing me more than $2,000+ per month out-of-pocket (Xolair & Tezspire).
Oral prednisone courses (no relief, nasty side effects)
None of them ever provided any meaningful relief. The inhaled steroids that should have been first-line treatment provided no meaningful improvement. Even after explicitly telling six different pulmonologists that "my inhaler isn't working," none ever mentioned theophylline or the concept of steroid resistance.
Research & Discovery
Then one day, while I was researching alternative options for fixing my shortness of breath, hoping I'd find something new (that I didn't already discover in my hundreds of searches & 12+ months of research before).
I came across Theophylline.
Once I looked deeper, what caught my attention was that theophylline doesn't just act as a bronchodilator. It also has the potential to reverse or restore steriod-resistance for people who don't respond to inhalers (it does this through HDAC activation mechanisms, separate from it's bronchodialating mechanism).
Theophylline belongs to the methylxanthine family (related to caffeine). At high doses of 800mg per day, it's often used for bronchodialation in COPD cases.
However, a only a small micro-dose of 100-200mg is needed to achieve the HDAC activation & re-sensitization effects.
The research is clear, and show us that Theophylline can:
Increase HDAC activity by 40-60%
Restore corticosteroid sensitivity in resistant inflammatory cells
Enhance anti-inflammatory effects of inhaled steroids by 3-5 fold
Reduce inflammatory gene expression independently of bronchodilation
The studies:
Implementation & Immediate Results
The next morning, I contacted my physician and requested a 30-day trial of theophylline 200mg daily. Unlike the weeks or months it usually took to rate some of the other interventions I've done, theophylline's effects were clear within days.
Day 1: Instant 50%+ improvement in breathing capacity.
Days 5-7: Effects became pronounced. My inhalers (previously useless) started to provide more noticeable relief.
Week 2: Objective improvements emerged:
Was able to go on my first short run in over 18 months!!!
Respiratory rate decreased to 13.2/minute (down from 14.4-15.2)
Walking tolerance increased from 25min on the treadmill, to 60min+ without issue
Subjective dyspnea improved by 95% (slight chest tightness, but breathing feels full & satisfying again).
Of all the interventions I'd tried—inhalers, antihistamines, montelukast, biologics—theophylline was by far the most impactful. But, it's real impact was made when used in combination with these first-line treatments together.
The Science Behind Why It Works
Based on my experience & research, here are some of the reasons theophylline may have worked so well for me.
1. HDAC2 Restoration
Post-viral illnesses & chronic oxidative stress (as seen in long covid) has been shown to down-regulate HDAC activity. Which is what leads to steriod-resistance.
Theophylline restores this HDAC function at low 100-200mg daily doses
This allows corticosteroids to suppress inflammatory genes effectively
2. Synergistic Anti-inflammatory Effects
Combination therapy produces effects greater than either medication alone
Neither medication alone was sufficient for meaningful improvement
2 Months Later: Sustained Improvement
Two months into treatment, my respiratory function remains stable at 95% of pre-COVID capacity.
My current protocol:
Theophylline: 200mg extended-release daily
Trelegy inhaler: Once daily
Montelukast 10mg: Once daily
Antihistamine (Levocetirizine): Once daily
Flonase Nasal Spray: Once day (helps improve nasal airflow).
Suplatast Tosilate: 3x daily (japanese anti-IGE allergy drug, which I have extremely high levels of in my last tests).
This combination approach has proven more effective than either medication alone, with Theophylline being one of the big final dominoes to fall towards recovery.
Side Effects?
Theophylline needs to be used with caution. It's a caffeine derivative, so it can have stimulating side effects. Luckily only small doses (1/8 the normal dose) are needed to achieve steriod-resensitization. Here's what I do to avoid side-effects.
Mild nausea (avoided if taken with food)
Insomnia (if taken late in the day). I take my dose immediately in the morning, with a meal.
Occasional palpitations at higher doses, or if mixing with other stimulants (avoid drinking too much coffee).
Drug interactions:
Antibiotics (Z-Pack) can double blood levels
Caffeine increases side effects
Cimetidine significantly elevates concentrations
Smoking reduces effectiveness
Final thoughts…
For long COVID patients, instead of assuming steroid resistance means "steroids don't work," we should ask "why don't steroids work, and how can we restore their effectiveness?"
Theophylline didn't cure my long COVID, but it restored something fundamental: the ability to breathe without conscious effort. More importantly, it revealed that the solution wasn't a newer, more targeted drug… it was understanding why existing treatments fail and exploring ways to restore their effectiveness.
This taught me that biological systems are more complex than what conventional medicine suggests. Asking questions, doing deeper research, and opening myself to testing new solutions — pays off.
If you want my one-on-one help creating a tailored recovery plan, schedule a call with me here.
