Vitamin D and Pulmonary Fibrosis: Does Vitamin D Deficiency Affect IPF?
Vitamin D is usually associated with bone health and calcium metabolism.
But vitamin D is also involved in:
immune regulation
inflammatory signaling
epithelial function
cellular differentiation
fibroblast biology
These functions have led researchers to investigate whether vitamin D could play a role in chronic lung diseases—including interstitial lung disease and pulmonary fibrosis.
The question has become particularly interesting because several studies have reported that patients with idiopathic pulmonary fibrosis, or IPF, who have low vitamin D levels may have:
worse lung function
greater disease severity
poorer survival
At the same time, experimental studies suggest that vitamin D can directly interfere with biological pathways involved in lung fibrosis.
Most recently, a 2026 experimental study found that vitamin D reduced pulmonary fibrosis by suppressing abnormal fibroblast metabolism through a newly described:
TK1 → PFKFB3 → glycolysis pathway. (PubMed)
This adds an interesting new mechanism to earlier research involving vitamin D receptor signaling and TGF-β-related fibrosis.
But an important distinction must be made:
Evidence that vitamin D deficiency is associated with pulmonary fibrosis does not prove that vitamin D supplementation treats pulmonary fibrosis.
At present, vitamin D should be considered an important nutritional and metabolic factor to assess and correct when deficient—not an established antifibrotic treatment.
What Is Vitamin D?
Vitamin D is a fat-soluble vitamin that also functions as a steroid-like hormone.
The two major forms are:
vitamin D2, or ergocalciferol
vitamin D3, or cholecalciferol
Vitamin D3 can be produced in the skin after ultraviolet-B exposure and can also be obtained from food or supplements.
Vitamin D undergoes several metabolic steps.
First, it is converted mainly in the liver to:
25-hydroxyvitamin D — 25(OH)D
This is the form generally measured in blood tests to assess vitamin D status.
It is subsequently converted to the biologically active hormone:
1,25-dihydroxyvitamin D — calcitriol.
The effects of calcitriol are mediated largely through the vitamin D receptor, or VDR, which is expressed in many tissues beyond bone—including immune and pulmonary cells. (PubMed)
Vitamin D Is More Than a Bone Vitamin
Vitamin D influences several biological processes relevant to pulmonary fibrosis.
These include:
innate immunity
adaptive immunity
inflammatory cytokines
oxidative stress
epithelial-cell biology
fibroblast activation
extracellular matrix production
This provides the biological rationale for studying vitamin D in fibrotic lung disease.
What Happens in Pulmonary Fibrosis?
Pulmonary fibrosis involves abnormal repair after lung epithelial injury.
A simplified sequence is:
alveolar epithelial injury ↓ abnormal repair signaling ↓ fibroblast activation ↓ myofibroblast formation ↓ collagen and extracellular matrix deposition ↓ progressive lung fibrosis
One of the central signaling molecules involved is:
TGF-β1
or transforming growth factor beta-1.
Vitamin D has been investigated because experimental evidence suggests it may interfere with several components of this fibrotic cascade.
Is Vitamin D Deficiency Common in Pulmonary Disease?
Low vitamin D levels are frequently reported across chronic respiratory diseases.
A major 2026 review published by the European Respiratory Society examined vitamin D across:
asthma
COPD
interstitial lung disease
lung cancer
tuberculosis
respiratory infections
The review concluded that vitamin D insufficiency is repeatedly associated with poorer respiratory outcomes.
However, it also emphasized an important problem:
clinical intervention trials have not consistently reproduced the benefits predicted by observational and mechanistic research. (PubMed)
This discrepancy is crucial when discussing vitamin D and pulmonary fibrosis.
Is Vitamin D Deficiency Associated With IPF?
Several observational studies suggest that it is.
One influential study examined vitamin D in patients with idiopathic pulmonary fibrosis and found that vitamin D deficiency correlated with several markers of disease severity.
Lower vitamin D was associated with poorer:
FVC
DLCO
and higher disease severity according to the GAP score.
Most notably, vitamin D deficiency was associated with increased all-cause mortality.
The reported hazard ratio was approximately:
HR 3.7
for mortality among vitamin D-deficient patients. (PubMed)
This is a substantial association.
But it requires careful interpretation.
Does Low Vitamin D Cause Worse IPF?
Not necessarily.
This is one of the central problems with observational nutrition research.
Low vitamin D could contribute biologically to disease.
But severe pulmonary fibrosis could also lead to low vitamin D.
For example, patients with more advanced disease may:
spend less time outdoors
receive less sunlight
exercise less
have poorer nutritional intake
have lower body weight or muscle mass
have more systemic illness
Therefore:
severe disease → lower vitamin D
is also possible.
The relationship may be bidirectional.
Could Vitamin D Simply Be a Marker of Overall Health?
Yes.
Vitamin D status can reflect multiple aspects of health and lifestyle.
Low 25(OH)D may sometimes act as a marker of:
frailty
nutritional status
reduced outdoor activity
chronic inflammation
comorbidity
Therefore, even a strong association between vitamin D deficiency and mortality does not prove that correcting vitamin D will reduce mortality.
This is why randomized trials are so important.
What Does Experimental Research Show?
Experimental research is considerably more supportive of a direct biological effect.
Vitamin D has demonstrated antifibrotic effects in:
cultured lung fibroblasts
animal pulmonary fibrosis models
Earlier experimental work suggested that vitamin D could interfere with fibroblast activation and extracellular matrix production.
The newest mechanistic research has expanded this considerably.
The Important 2026 Vitamin D–Pulmonary Fibrosis Study
A study published in the Journal of Translational Medicine in April 2026 investigated how vitamin D affects fibroblast metabolism during pulmonary fibrosis.
Researchers studied:
human MRC-5 lung fibroblasts
primary mouse lung fibroblasts
experimental pulmonary fibrosis models
They focused particularly on abnormal glucose metabolism within activated fibroblasts. (PubMed)
Why Is Fibroblast Metabolism Important?
Activated fibroblasts require substantial energy to:
proliferate
differentiate
produce collagen
synthesize extracellular matrix
Fibrotic fibroblasts undergo metabolic reprogramming.
One important change is increased:
glycolysis
—the cellular pathway used to metabolize glucose.
This metabolic shift helps support the energy requirements of activated myofibroblasts.
Therefore, abnormal fibroblast metabolism itself may become a therapeutic target.
Vitamin D and Glycolysis
The 2026 study identified an important pathway involving:
thymidine kinase 1 — TK1
and
PFKFB3
a major regulator of glycolysis.
Researchers found that TGF-β1 increased TK1.
TK1 promoted PFKFB3-driven glycolysis.
This supported fibroblast activation and pulmonary fibrosis.
Vitamin D inhibited this pathway. (PubMed)
The proposed sequence was:
Vitamin D ↓ TK1 inhibition ↓ PFKFB3 suppression ↓ reduced glycolysis ↓ reduced fibroblast activation ↓ less experimental pulmonary fibrosis
This provides a novel metabolic explanation for vitamin D’s potential antifibrotic effects.
Why Is PFKFB3 Important?
PFKFB3 is an important regulator of cellular glycolysis.
Fibroblasts undergoing activation may depend increasingly on glycolytic metabolism.
Therefore, reducing PFKFB3 activity could potentially reduce the metabolic capacity required for fibroblasts to become collagen-producing myofibroblasts.
This concept fits into a much broader area of modern fibrosis research:
metabolic reprogramming in pulmonary fibrosis.
Vitamin D and TGF-β
TGF-β is one of the major drivers of pulmonary fibrosis.
It promotes:
fibroblast activation
myofibroblast differentiation
collagen production
extracellular matrix deposition
Earlier experimental research has suggested that vitamin D/VDR signaling can interfere with TGF-β-related fibrotic pathways.
The new metabolic evidence adds another layer to this interaction.
Vitamin D may therefore influence fibrosis through multiple mechanisms rather than a single signaling pathway.
Vitamin D Receptor and Fibroblasts
The biological effects of active vitamin D are largely mediated through the vitamin D receptor.
When activated, VDR can influence transcription of numerous genes.
Experimental fibrosis research suggests that adequate VDR signaling may help oppose some profibrotic transcriptional programs.
This has generated interest in the VDR as a potential therapeutic target.
But VDR-targeted antifibrotic therapy remains experimental.
Vitamin D and Collagen Production
One of the hallmarks of pulmonary fibrosis is excessive collagen deposition.
Experimental vitamin D studies have reported reductions in:
collagen synthesis
fibroblast proliferation
myofibroblast differentiation
These findings support an antifibrotic biological effect.
But again, this evidence is mainly derived from laboratory and animal studies.
Vitamin D and the Immune System
Vitamin D also has substantial immunomodulatory effects.
It can influence:
macrophages
dendritic cells
T lymphocytes
regulatory T cells
inflammatory cytokines
These effects may be particularly relevant in inflammatory or autoimmune forms of ILD.
However, IPF is no longer considered primarily an inflammatory disease.
The central pathology involves epithelial injury and abnormal fibrotic repair.
Therefore, vitamin D’s potential relevance to IPF probably extends beyond its anti-inflammatory properties.
Vitamin D and Oxidative Stress
Oxidative stress contributes to epithelial injury and fibroblast activation.
Experimental studies suggest vitamin D may influence antioxidant pathways and cellular responses to oxidative stress.
This provides another potential connection between vitamin D deficiency and fibrotic biology.
Vitamin D and Epithelial Cells
Pulmonary fibrosis is increasingly understood as a disease involving dysfunctional alveolar epithelial repair.
Vitamin D receptors are present in epithelial tissues.
Vitamin D may influence:
epithelial differentiation
barrier function
immune responses
cellular survival
Whether correcting vitamin D deficiency improves alveolar epithelial repair in human IPF remains unknown.
Vitamin D and Cellular Senescence
Cellular senescence is increasingly recognized as an important mechanism in IPF.
Senescent alveolar epithelial cells can release inflammatory and profibrotic mediators known collectively as the:
senescence-associated secretory phenotype, or SASP.
Vitamin D has been investigated in cellular aging and oxidative stress pathways.
However, direct evidence that vitamin D supplementation modifies pulmonary cellular senescence in patients with IPF is currently insufficient.
Vitamin D and Autophagy
Autophagy allows cells to remove:
damaged proteins
dysfunctional organelles
cellular debris
Impaired autophagy is implicated in pulmonary fibrosis.
Vitamin D signaling may interact with cellular metabolic and autophagy pathways.
This represents another mechanistic area worthy of investigation, but it has not yet produced an established vitamin D-based IPF therapy.
What About Autoimmune Interstitial Lung Disease?
Vitamin D becomes particularly interesting when ILD occurs in autoimmune disease.
Examples include:
systemic sclerosis
rheumatoid arthritis
inflammatory myositis
antisynthetase syndrome
Sjögren disease
Vitamin D has immunomodulatory properties, and deficiency is common in several autoimmune conditions.
Systemic sclerosis provides particularly interesting data.
Vitamin D and Systemic Sclerosis
A 2024 systematic review, meta-analysis and meta-regression examined vitamin D in systemic sclerosis.
The analysis found that lower vitamin D levels were associated with:
susceptibility to systemic sclerosis
occurrence of interstitial lung disease
higher systolic pulmonary arterial pressure
greater skin involvement
Specifically, lower vitamin D was significantly associated with the occurrence of ILD. (PubMed)
This is important observational evidence.
But once again:
association does not demonstrate that vitamin D supplementation prevents or treats SSc-ILD.
Vitamin D and Pulmonary Hypertension in Systemic Sclerosis
The same meta-analysis reported an association between vitamin D deficiency and higher estimated systolic pulmonary artery pressure. (PubMed)
This is interesting because systemic sclerosis can cause pulmonary vascular disease as well as ILD.
However, vitamin D should not be considered a treatment for pulmonary hypertension on the basis of this association.
Why Could Vitamin D Be Low in Systemic Sclerosis?
Potential contributors include:
reduced sun exposure
gastrointestinal involvement
malabsorption
dietary factors
chronic inflammation
medication effects
reduced physical activity
Therefore, vitamin D deficiency may be both a biological factor and a consequence of chronic systemic disease.
Does Vitamin D Supplementation Treat Pulmonary Fibrosis?
At present:
No clinical evidence demonstrates that vitamin D supplementation is an established treatment for pulmonary fibrosis.
This is the most important clinical message.
The 2026 ERS review emphasizes that although mechanistic and observational evidence is compelling in several respiratory diseases, intervention studies have produced mixed results. (PubMed)
Large, well-designed randomized trials specifically targeting vitamin D-deficient patients with pulmonary fibrosis are still needed.
Does Vitamin D Reverse Lung Fibrosis?
There is no evidence that oral vitamin D supplementation reverses established pulmonary fibrosis in humans.
Experimental reduction of fibrosis in mice should not be interpreted as evidence of reversal in human IPF.
Should Vitamin D Deficiency Still Be Corrected?
Yes—when a patient is genuinely deficient, vitamin D has established health implications independent of pulmonary fibrosis.
Vitamin D is important for:
bone health
calcium metabolism
muscle function
These are particularly relevant in chronic lung disease.
Patients with advanced ILD may already be vulnerable to:
physical deconditioning
muscle weakness
falls
osteoporosis
Some may also receive corticosteroids, depending on the ILD subtype, which can further increase bone risk.
Correcting deficiency is therefore clinically reasonable even without claiming an antifibrotic effect.
Vitamin D, Muscle and Pulmonary Rehabilitation
This is an often overlooked area.
Pulmonary fibrosis reduces exercise capacity.
Reduced activity contributes to:
deconditioning → muscle loss → poorer exercise tolerance
Vitamin D deficiency may contribute to impaired musculoskeletal health.
Therefore, correcting deficiency may support the broader goals of:
maintaining muscle
preserving mobility
supporting rehabilitation
protecting bone
These are clinically meaningful outcomes even if vitamin D does not alter fibrosis itself.
What Vitamin D Test Should Be Measured?
The standard clinical test for vitamin D status is:
serum 25-hydroxyvitamin D — 25(OH)D.
Routine measurement of 1,25-dihydroxyvitamin D is generally not the appropriate test for assessing ordinary vitamin D nutritional status.
What Level Is Considered Deficient?
Definitions vary between professional organizations and clinical contexts.
Historically, concentrations below approximately 20 ng/mL have commonly been classified as deficient in many clinical frameworks.
However, debates continue regarding:
optimal thresholds
population screening
ideal targets
For pulmonary fibrosis specifically, no evidence-based “antifibrotic vitamin D level” has been established.
This point is important.
There is no validated target such as:
“Vitamin D must be above X to slow IPF.”
Is More Vitamin D Better?
No.
Vitamin D is fat-soluble.
Excessive supplementation can cause toxicity.
Potential consequences include:
hypercalcemia
kidney stones
kidney injury
gastrointestinal symptoms
neurological symptoms
Therefore, supplementation should be based on appropriate clinical assessment rather than the assumption that higher levels produce greater antifibrotic effects.
What About Vitamin D3 With Vitamin K2?
Vitamin D3 and vitamin K2 are frequently combined in supplements.
Vitamin K has important roles in coagulation and bone metabolism.
But there is no clinical evidence showing that combining vitamin D3 with K2 provides an antifibrotic treatment for IPF.
Patients taking anticoagulants, particularly vitamin K antagonists, should also discuss vitamin K supplementation with their treating clinician.
Can Sunlight Replace Supplements?
Sun exposure can contribute to vitamin D production.
But vitamin D synthesis varies according to:
season
latitude
skin pigmentation
clothing
age
time outdoors
Patients with advanced pulmonary disease may also spend less time outdoors.
Therefore, blood testing can be more informative than assuming sun exposure is adequate.
Vitamin D and the Gut Microbiome
Vitamin D and the intestinal microbiome may also interact.
Vitamin D receptor signaling can influence:
intestinal epithelial function
mucosal immunity
microbial ecology
Conversely, the microbiome may influence host immune and metabolic responses.
This raises an interesting possibility that vitamin D could interact with the gut–lung axis.
However, there is currently insufficient evidence to claim that vitamin D improves pulmonary fibrosis through microbiome modification.
Could Vitamin D Become a Precision Treatment?
Potentially—but probably not as simple supplementation.
The new 2026 study suggests that specific metabolic pathways such as:
TK1 → PFKFB3 → glycolysis
could potentially become therapeutic targets. (PubMed)
Future research may therefore focus on:
VDR agonists
fibroblast metabolism
PFKFB3
vitamin D-responsive molecular phenotypes
rather than simply giving higher doses of conventional vitamin D.
Why Randomized Trials Are Needed
The ideal clinical trial would enroll patients with:
confirmed pulmonary fibrosis
documented vitamin D deficiency
and randomize them to standardized replacement versus appropriate control.
Important outcomes would include:
FVC decline
DLCO
HRCT fibrosis
exercise capacity
quality of life
exacerbations
survival
It should also evaluate whether outcomes differ according to:
IPF versus autoimmune ILD
baseline vitamin D level
VDR genetics
antifibrotic therapy
immune phenotype
Until such trials are performed, vitamin D remains a promising biological factor rather than a proven disease-modifying therapy.
Functional and Integrative Medicine Perspective
Vitamin D is highly relevant to integrative pulmonary care—but precision in interpretation is essential.
A reasonable comprehensive assessment may consider:
serum 25(OH)D
nutritional intake
bone health
muscle mass
physical activity
gastrointestinal absorption
medications
autoimmune disease
If deficiency is present, it should be appropriately addressed.
But correcting deficiency should be presented as:
optimizing nutritional and musculoskeletal health
rather than:
treating pulmonary fibrosis with vitamin D.
This distinction protects patients from unrealistic expectations while still recognizing potentially important modifiable factors.
What We Know
We know that vitamin D:
has immunomodulatory biological effects
influences fibroblast biology experimentally
can reduce experimental pulmonary fibrosis
is frequently low in chronic respiratory disease
has been associated with FVC, DLCO and mortality in IPF observational research
is associated with SSc-ILD occurrence in recent meta-analysis
can suppress TK1/PFKFB3-driven glycolysis and fibroblast activation experimentally
(PubMed)
What We Do Not Know
We do not know whether vitamin D supplementation:
slows FVC decline in IPF
improves DLCO
prevents fibrosis progression
reverses established fibrosis
reduces mortality
improves SSc-ILD
enhances antifibrotic treatment
These remain unanswered clinical questions.
What Does This Mean Clinically?
The most evidence-based interpretation is:
Vitamin D deficiency should be identified and appropriately corrected for established nutritional, bone and musculoskeletal reasons, particularly in patients with chronic lung disease.
But vitamin D supplementation should not currently be presented as an antifibrotic therapy.
This approach recognizes the biological evidence without exceeding it.
Frequently Asked Questions
Is vitamin D deficiency common in pulmonary fibrosis?
Low vitamin D levels have been reported in IPF and other chronic respiratory diseases, although prevalence varies between populations.
Is low vitamin D associated with worse IPF?
Yes. Observational research has linked vitamin D deficiency with lower FVC and DLCO, greater disease severity and increased mortality. (PubMed)
Does that mean vitamin D deficiency causes pulmonary fibrosis?
No. Association does not establish causation.
Can vitamin D reverse pulmonary fibrosis?
There is currently no human clinical evidence that vitamin D supplementation reverses established pulmonary fibrosis.
Does vitamin D reduce fibrosis in animals?
Yes. Experimental studies have demonstrated antifibrotic effects.
What did the new 2026 study find?
It found that vitamin D inhibited fibroblast activation and experimental pulmonary fibrosis partly by suppressing TK1/PFKFB3-driven glycolysis. (PubMed)
Is vitamin D linked with systemic sclerosis-associated ILD?
A recent meta-analysis found lower vitamin D levels associated with the occurrence of ILD in systemic sclerosis. (PubMed)
Should patients with pulmonary fibrosis check vitamin D?
Vitamin D assessment can be clinically appropriate, particularly when there are risk factors for deficiency, poor nutrition, osteoporosis, reduced sunlight exposure or other indications.
What vitamin D level stops fibrosis?
No such level has been established.
Should patients take high-dose vitamin D for IPF?
High-dose vitamin D should not be used as an unproven treatment for IPF. Excess vitamin D can cause toxicity.
Key Takeaway
Vitamin D is biologically interesting in pulmonary fibrosis.
Experimental evidence suggests that it can influence:
fibroblast activation + TGF-β signaling + cellular metabolism + inflammatory pathways
and newer research has identified TK1/PFKFB3-mediated glycolysis as another potential mechanism. (PubMed)
Human observational studies also associate low vitamin D with poorer IPF outcomes.
But the missing piece remains the most clinically important one:
we do not yet have convincing human trial evidence that vitamin D supplementation slows pulmonary fibrosis.
Conclusion
Vitamin D occupies an interesting position between nutritional medicine and pulmonary fibrosis biology.
It is clearly more than a regulator of calcium and bone metabolism.
Vitamin D receptors are widely distributed, and vitamin D can influence immune signaling, fibroblast behavior, cellular metabolism and potentially several pathways involved in fibrosis.
Human observational evidence has provided important signals.
One IPF study found vitamin D deficiency associated with lower FVC, lower DLCO, greater GAP disease severity and substantially higher all-cause mortality. (PubMed)
In systemic sclerosis, a recent systematic review and meta-analysis found that lower vitamin D levels were associated with the occurrence of ILD as well as other markers of disease severity. (PubMed)
The experimental evidence has also continued to evolve.
Most notably, a 2026 study identified a novel metabolic pathway through which vitamin D suppressed fibroblast activation:
Vitamin D → inhibition of TK1 → reduction in PFKFB3-driven glycolysis → decreased fibroblast activation → reduced experimental fibrosis. (PubMed)
This is particularly interesting because modern pulmonary fibrosis research increasingly recognizes metabolic reprogramming of fibroblasts as part of fibrogenesis.
But the clinical evidence remains behind the mechanistic science.
The European Respiratory Society’s 2026 review of vitamin D in pulmonary disease emphasized this wider problem: observational and mechanistic studies frequently suggest benefit, while randomized clinical trial evidence remains inconsistent. (PubMed)
Therefore, the most scientifically defensible conclusion is not that vitamin D “treats pulmonary fibrosis.”
It is that:
vitamin D deficiency may represent an important biological, nutritional and prognostic factor that deserves appropriate assessment in patients with chronic lung disease, while its role as a disease-modifying treatment remains unproven.
For patients with pulmonary fibrosis, correcting genuine deficiency may support:
bone health
muscle function
nutritional status
rehabilitation
overall health
These outcomes matter.
But vitamin D should not replace established treatment such as antifibrotic therapy for appropriate patients with IPF or immunomodulatory treatment for selected autoimmune-associated ILD.
The next phase of research should determine whether carefully selected vitamin D-deficient pulmonary fibrosis patients represent a phenotype in which targeted correction produces measurable pulmonary benefit.
Until then, the appropriate approach is:
test when clinically appropriate, correct deficiency responsibly, and avoid turning promising mechanistic evidence into an unproven antifibrotic claim.
About Dr. Samar Shadly
Dr. Samar Shadly is a Consultant Pulmonologist and Certified Functional Medicine Practitioner, with advanced subspecialty training in interstitial lung disease, pulmonary fibrosis, pulmonary hypertension and lung transplantation at the University of Toronto.
Her clinical and academic interests include Integrative and Functional Pulmonology, pulmonary fibrosis, autoimmune-associated ILD, the gut–lung axis, nutrition, metabolic health and emerging microbiome research.
Looking for a Comprehensive Approach to Pulmonary Fibrosis or ILD?
A comprehensive assessment of pulmonary fibrosis may include not only the lung disease itself, but also clinically relevant factors such as:
nutritional status
vitamin and mineral deficiencies
gastrointestinal health
reflux
muscle mass
metabolic health
lifestyle factors
These factors should be addressed alongside—not instead of—appropriate pulmonary and rheumatological treatment.
Contact us through the consultation page or WhatsApp to learn more about online consultation options.
Functional and integrative care should complement—not replace—evidence-based pulmonary treatment.
Medical Disclaimer: This article is for educational purposes only and does not constitute individualized medical advice. Vitamin D is not currently an established treatment for pulmonary fibrosis.