SYSTEMATIC REVIEW

EFFECTS OF VITAMIN D ON RESPIRATORY FUNCTION AND IMMUNE STATUS FOR PATIENTS

WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): A SYSTEMATIC REVIEW

Sikandar Ali Khan¹, Hina Hakeem¹, Farzana Salman², Shamaila Wadud², Sara Yar Khan¹, Momina Haq²

How to cite this article

ABSTRACT

OBJECTIVES

Khan S A, Hakeen H, Salman F,

Wadud S, Khan S Y, Haq M. Effects

of Vitamin D on Respiratory Function

and Immune Status for Patients with

Chronic Obstructive Pulmonary

Disease (Copd): A Systematic Review.

J Gandhara Med Dent Sci. 2026;13(3):

128-138.

To systematically review recent evidence on the eects of vitamin D on

respiratory function and immune status in patients with COPD.

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory

disorder characterized by persistent airow limitation, recurrent

exacerbations, systemic inammation, and impaired quality of life. Vitamin D

has immunomodulatory and anti-inammatory eects and has been

investigated for its possible role in COPD progression and clinical outcomes.

METHODOLOGY

Eligible studies were identied through searches of PubMed, Web of Science,

and Scopus. Search terms included vitamin D, COPD, respiratory function,

inammation, and immune status. Original human studies published between

2020 and 2025 were included. Eligible study designs included randomized

controlled trials, cohort studies, case-control studies, longitudinal studies, and

cross-sectional studies. Reviews, meta-analyses, pilot studies, case reports,

case series, editorials, conference abstracts, and animal studies were excluded.

Study selection was conducted according to PRISMA 2020 guidelines. Data

were extracted narratively, and methodological quality was assessed using the

Cochrane Risk of Bias 2 tool and Joanna Briggs Institute appraisal checklists.

RESULTS

A total of 512 records were identied, of which 18 original studies met the

eligibility criteria for qualitative synthesis. Most studies showed that low serum

25-hydroxyvitamin D levels were associated with poorer lung function, greater

symptom burden, increased risk of acute exacerbations, and higher

inammatory activity in COPD. Evidence from supplementation trials was

inconsistent. Some studies reported improvement in exacerbation frequency

and symptom scores, whereas others found no signicant overall benet.

CONCLUSION

https://doi.org/10.37762/jgmds.13-3.890

Date Submission:

Date Revised:

10-03-2026

22-05-2026

Date Acceptance: 22-05-2026

²Professor, Department of Physiology,

Peshawar Medical College, Peshawar

Correspondence

¹Hina Hakeem, Assistant Professor

Department of Biochemistry, Peshawar

Medical College, Peshawar

+92-345-0526117

hinahakeem4@gmail.com

Low vitamin D status appears to be associated with adverse respiratory and

immune-inammatory outcomes in patients with COPD. Current evidence

does not support universal vitamin D supplementation for all COPD patients;

however, assessment and correction of deciency may be useful in selected

high-risk or decient patients. Further large, well-designed trials are needed

to clarify the clinical relevance of vitamin D in COPD.

KEYWORDS: Chronic Obstructive Pulmonary Disease, Vitamin D,

Respiratory Function, Immune Status, Inammation, Systematic Review

outcomes and extrapulmonary complications.²Vitamin

D is traditionally known for its role in calcium

INTRODUCTION

regulation and bone health. However, recent evidence

indicates that it also plays an important role in immune

regulation, inammation control, and protection against

respiratory infections.³Vitamin D receptors are present

on several immune and respiratory cells. Vitamin D

signaling may help regulate cytokine activity, oxidative

stress, and susceptibility to infection. These eects are

particularly relevant in COPD, where repeated

infections and persistent airway inammation

Chronic obstructive pulmonary disease (COPD) is a

chronic respiratory disease characterized by persistent

airflow limitation, progressive respiratory symptoms,

recurrent exacerbations, and reduced functional

capacity and quality of life.¹In addition to pulmonary

impairment, COPD is increasingly recognized as a

systemic

condition

associated

with

chronic

inflammation, oxidative stress, skeletal muscle

dysfunction, and nutritional disturbances. These

contribute

disease

severity

and

frequent

interacting

mechanisms

contribute

disease

progression and may inuence both respiratory

exacerbations.^4,5Many patients with COPD have low

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J Gandhara Med Dent Sci

128

Eects of Vitamin D on Respiratory Function and Immune Status for Patients

serum vitamin D levels, and this deciency has been

outcomes. Respiratory outcomes included lung

function indices, respiratory symptoms, emphysema

progression, disease severity, acute exacerbations,

emergency visits, and other COPD-related clinical

indicators. Immune and inammatory outcomes

included C-reactive protein, interleukins, inammatory

associated with poorer lung function, greater symptom

burden, more frequent exacerbations, and unfavorable

clinical outcomes. However, the benet of vitamin D

supplementation in COPD remains uncertain, as

clinical trials and review studies have reported

inconsistent ndings. Some studies suggest that

supplementation may be more useful in patients with

marked vitamin D deciency or a high risk of

exacerbations, while routine supplementation for all

COPD patients is not consistently supported by current

evidence.^4,6,7,8Recent studies dier in their design,

signaling pathways, vitamin

receptor-related

ndings, and T-lymphocyte parameters. The inclusion

criteria comprised original human studies conducted on

patients diagnosed with COPD, published between

2020 and 2025, that assessed serum or plasma vitamin

D levels, vitamin D deciency, or vitamin D

supplementation, and that reported respiratory function,

clinical respiratory outcomes, immune status, or

inflammatory markers. Randomized controlled trials,

cohort studies, case-control studies, longitudinal

studies, prospective observational studies, and cross-

sectional studies were included when full-text articles

were available in English. The exclusion criteria

included systematic reviews, meta-analyses, narrative

reviews, pilot studies, case reports, case series,

editorials, letters, conference abstracts, animal studies,

and in vitro studies. Articles were also excluded if they

did not include COPD patients, did not assess vitamin

D status or supplementation, did not report respiratory

or immune-related outcomes, or had insucient data

relevant to the review question. All records retrieved

from the databases were imported into the screening

process, and duplicate articles were removed. A total of

512 records were initially identied through database

searching. After removing duplicates and other clearly

ineligible articles, 408 records remained for title and

abstract screening. Of these, 344 records were excluded

during the initial screening phase. Sixty-four reports

were sought, of which four could not be retrieved.

Therefore, 60 full-text articles were assessed for

eligibility. After full-text review, 42 articles were

excluded because they had an ineligible study design,

were review-type articles or case reports, or did not

report outcomes relevant to the review question.

Finally, 18 original studies fullled the eligibility

criteria and were included in the qualitative synthesis.

The study selection process was documented using a

PRISMA 2020 ow diagram. Data were extracted

using a structured data extraction form. The extracted

information included author name, year of publication,

country or study setting, study design, sample size,

characteristics of the COPD population, type of vitamin

D exposure or intervention, and the main respiratory,

immune, and inammatory outcomes. Additional

information was also extracted regarding exacerbation

frequency, lung function parameters, symptom scores,

inflammatory markers, T-lymphocyte ndings, and the

effects of supplementation. The extracted data were

organized into summary tables showing study

outcome

measures,

patient

populations,

and

interpretation of respiratory and immune-related

ndings. Therefore, a focused review of recent

evidence is needed. The objective of this systematic

review was to evaluate the eects of vitamin D on

respiratory function and immune status in patients with

COPD by reviewing original studies published between

2020 and 2025.

METHODOLOGY

This systematic review was conducted to evaluate the

association of vitamin D status and supplementation

with respiratory function and immune-related outcomes

in patients with chronic obstructive pulmonary disease

(COPD). Original human studies were reviewed and

summarized to determine how serum vitamin D levels

or vitamin D replacement were related to clinically

relevant COPD outcomes. Because of dierences in

study design, population characteristics, vitamin D

assessment, intervention protocols, and outcome

measures,

meta-analysis was not performed.

Therefore, the ndings were synthesized narratively. A

structured literature search was performed using three

electronic databases: PubMed, Web of Science, and

Scopus. The search was limited to articles published

from 2020 to 2025 to include recent evidence. Search

terms were developed according to the main concepts

of the review and included “vitamin D,” “25-

hydroxyvitamin D,” “chronic obstructive pulmonary

disease,” “COPD,” “respiratory function,” “lung

function,” “FEV1,” “immune status,” “inammation,”

and “exacerbation.” Boolean operators such as AND

and OR were used to combine relevant terms. In

addition, the reference lists of selected articles were

manually reviewed to identify any eligible studies that

may have been missed during database searching.

Eligibility criteria were dened before screening.

Studies were considered eligible if they were original

human studies involving patients with COPD and

assessed serum or plasma vitamin D levels, vitamin D

deciency, or vitamin D supplementation in relation to

respiratory, clinical, immune, or inammatory

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Eects of Vitamin D on Respiratory Function and Immune Status for Patients

characteristics, respiratory outcomes, immune and

RESULTS

inflammatory outcomes, and methodological quality.

The methodological quality of the included studies was

assessed according to study design. Randomized

controlled trials were evaluated using the Cochrane

Risk of Bias 2 tool, while observational studies were

assessed using the relevant Joanna Briggs Institute

critical appraisal checklists. Each study was reviewed

for possible sources of bias, including selection bias,

confounding, measurement bias, lack of temporality,

Table 1 presents the main characteristics of the 18

original studies included in this systematic review. The

included studies were published between 2020 and

2025 and were conducted in dierent countries,

including the USA, Turkey, South Korea, Belgium,

Germany, China, India, Spain, the Netherlands, South

Africa, and Romania. Most studies were observational,

including cross-sectional, cohort, longitudinal, and

prospective designs. The review also included one case-

control study and two randomized controlled trials.

Sample sizes varied across studies, ranging from 65

patients in acute exacerbation settings to 1,876 COPD

patients in secondary database analyses. Most studies

assessed baseline serum or plasma 25-hydroxyvitamin

D [25(OH)D] as the main exposure, while two

randomized controlled trials evaluated the eect of

vitamin D3 supplementation in vitamin D-decient

COPD patients. The main outcomes reported across the

studies included lung function indices, respiratory

symptom burden, emphysema progression, frequency

of acute exacerbations, inammatory markers, T-

lymphocyte status, and all-cause mortality. Overall, the

included studies showed that lower vitamin D levels

were generally associated with poorer respiratory

performance, increased inammatory activity, and a

higher risk of exacerbations in COPD. However, the

incomplete

outcome

reporting,

and

limited

generalizability. The overall risk of bias was

categorized as low, moderate, or high. A narrative

synthesis approach was used for data analysis. Findings

were grouped into the main themes of the review:

general study characteristics, respiratory function and

clinical

respiratory

outcomes,

immune

and

inflammatory ndings, and methodological quality.

Particular attention was given to the consistency of

associations between low vitamin D status and adverse

COPD outcomes, as well as the direction of eect

reported in vitamin D supplementation trials. Due to

heterogeneity in study designs, outcome denitions,

laboratory measures, and intervention protocols,

quantitative pooling of results was considered

inappropriate.

evidence regarding the benet of vitamin

supplementation was not fully consistent.

Identication of studies via databases and registers

Records removed before screening:

Records identied from*:

PubMed: 214

Web of Science: 154

Scopus: 144

Duplicate records removed (n=96)

.Records marked as ineligible by

automation tools (n=0)

.Records removed for other resons

(n=08)

Table 1: Characteristics of original studies included in the

systematic review

Study Country Study COPD Vitamin Mainoutco Key

/setting design populat D expos mes repor nding

Records excluded**

(n = 344)

Records screened

(n = 408)

ion

ure/inter ted

vention

relevan

t to rev

iew

Records sought for retrieval

(n = 64)

Reports not retrieved

(n = 4)

Burke USA,

Observ Adults

Baseline Lung funct Lower

serum 25 ion, prior 25(OH)

(OH) D exacerbati D was

ons, longit associat

s et al., SPIRO ational with

2020 MICS

[9]

cohort COPD

analysis (SPIRO

cohort

Reports assessed for eligibility

(n = 60)

Report excluded:

Not qualitative: 14

Case reports/reviwes: 17

Irrelevant Outcomes: 11

Total excluded: 42

udinal outc ed with

MICS;

n=1609)

omes

worse

lung fu

nction

and

with

worse

lung fu

nction

and

Studied included in qualitative synthesis

(n = 18)

greater

exacer

bation

burden

Figure 1: PRISMA-based study selection ow chart for the

systematic review of vitamin D and COPD outcomes. The database

search yielded 512 records. After removal of duplicates and other

ineligible records, 408 articles proceeded to title and abstract

screening. Full texts of 60 potentially relevant articles were assessed

for eligibility. Finally, 18 original studies met the inclusion criteria

and were included in the qualitative synthesis.

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Eects of Vitamin D on Respiratory Function and Immune Status for Patients

Köktürk Turkey,

Cross-

hospitaliz sectional alized vitamin in D def n D def

ed patients observati COPD iciency iciency

Hospit Serum Vitam Vitami

Lokesh India

et al.,

Case-contr COPD Serum

COPD Vitamin

et al.,

2020

[10]

ol study

patients vitamin D presence D deci

and con deciency and exa ency

2021

onal study patien status prevalen was hi

[15]

trols

n=100

cerbatio was ass

n status ociated

with C

ts n=1

ce, clini ghly

cal serve prevale

rity prof nt in ho

OPD

ile

spitaliz

ed CO

PD pat

ients

and wit

h exace

rbation

risk

Calle

Spain,

Cross-secti High- Vitamin High- Vitamin

Kim et South

al., 2020 Korea

[11]

Longitudi Male Plasma Emphys Severe

nal obser COPD 25(OH) ema ser vitamin

vational patien D level verity/pr D dec

Rubio outpatie onal study risk CO D testing risk

D deci

COP

et al., nt clinics

2022

[16]

PD outp serum

atient levels

n=97

preval ency/in

ence of sucie

decien ncy was

study

ts (n=1

51)

ogressio incy w

as asso

ciated

with e

mpyse

ma pro

gressio

cy.

commo

n in hig

h -risk

outpatie

nt COP

popu

lations.

Mathyss Belgium

en et al.,

2020

Translatio COPD Vitamin Airway COPD

nal obse airway D-relate vitamin airways

observatio tissue d gene e D pathw showed

nal study sample xpressio ay mark altered

Lee et South

Cross-secti Stable Serum

CAT

Vitamin

al., 2022 Korea onal study COPD vitamin D score, D insu

patients level

n=329

respirato ciency/

ry sympt decien

[17]

[12]

s/patie

nts

ers

local vi

tamin

oms

cy was

associat

ed with

worse

respirat

ory sym

ptoms.

D-relat

ed gene

express

ion, su

pportin

g biolo

gical pl

ausibilt

y for

Raq et Netherla Randomize Vitamin Vitamin D Exacerb Supple

al.,

2022

[18]

nds

d controlle D-deci supplemen ation rat mentati

d trail

ent COP tation

D patien

ts n=115

e, pulmo on did

nary fun not sign

ction, m icantly

uscle str reduce

ength, the over

inamm all exac

atory ma erbation

rkers, Q rate in d

immun

e eect

Jorde et Germany Cohort

al., 2021

[13]

COPD Serum Disease Lower

cohort 25(OH) severity, vitamin

n=94

study

CRP,

IL-6,

prior FE with

D was

linked

ecien.

t COPD

patients

Lower

V1 decli greater

ne, exac disease

erbation severit

Wang et China Cross-secti Patients Serum

CAT

onal study

al.,

with acu vitamin D score, vitamin

2023

y, ina

mmatio

n, and

exacerb

ation re

-lated

te exace and IL-1β inamm D and

[19]

rbation

of COP

D n=65

atory

status

higher

IL-β co

rretaled

with w

orse sy

mptom

burden

in AEC

OPD

outcom

Fu et al.,

2021

[14]

Patients Serum Inamm Low

with C vitamin atory ma vitamin

China

Observati

onal study

OPD D status rkers

n=101

D statu

s was a

ssociat

ed with

systemi

c ina

mmatio

in COP

Kola et South

Prospective

Serum

Decien

COPD

Decie

al.,

Africa, cross-sectio

tertiary nal study

hospital

2024

vitamin D

status

patients

at Chris

Hani Ba

ragwana

th Hospi

tal n=76

cy preva ncy and

lence an insuc

d associ iency w

ated cha ere com

ractristic mon am

[20]

ong CO

PD pati

ents in

this tert

July - September 2026

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131

Eects of Vitamin D on Respiratory Function and Immune Status for Patients

ction u

p to a

thres

iary-car

e Afric

an coho

everity

hold .,

invers

L-shap

ed rela

tionshi

p obser

ved

Jiang et USA,

al., 2024 NHANE analysis

[21]

Cohort

COPD Serum 25 All-caus Higher

patients (OH) D e mortali vitamin

(n=1876

)

D level

s were

associa

ted non

linearly

with lo

wer all-

cause

mortali

ty in C

OPD.

Rus et Romania Observatio Patients Serum

COPD Lower

al.,

with ac vitamin D severity, vitamin

ute exac during AE inamm D durin

2025

nal study

[26]

erbation during

of COP COPD

D n=10

tory pro g exace

le

rbation

was ass

ociated

with ve

ry seve

re COP

Lakra et India,

Randomize Stable C Vitamin Acute Supple

al.,

tertiary d controlled OPD pa D3 supple exacerba mentati

2025

[22]

care

center

trail

tients w mentation tions, C on redu

ith hypo

vitamin

osis D3

(n=100)

AT scor ced acu

e, emerg te exac

ency visi erbation

25(OH)D = 25-hydroxyvitamin D; AECOPD = acute exacerbation of

chronic obstructive pulmonary disease; CAT= COPDAssessmentTest;

COPD = chronic obstructive pulmonary disease; CT = computed

tomography; FEV1 = forced expiratory volume in 1 second; FVC =

forced vital capacity;QoL= quality of life.

s, impr

oved C

AT scor

es, and

reduced

emerge

ncy visi

ts in de

cient

patient

Table 2 summarizes the respiratory function and

clinical respiratory outcomes reported in the included

original studies. Most observational studies showed that

low serum vitamin D levels were associated with poorer

lung function, greater respiratory symptom burden,

emphysema progression, and an increased risk of acute

exacerbations in patients with COPD. However, the

ndings from vitamin D supplementation trials were

not uniform. One randomized controlled trial reported

no signicant overall improvement in exacerbation rate

or pulmonary function, whereas another trial showed

reduced exacerbations, improved CAT scores, and

fewer emergency visits among vitamin D-decient

COPD patients. These ndings suggest that the

respiratory benet of supplementation may depend on

baseline vitamin D status and patient risk prole.

Jiang et China Cross

COPD Serum

COPD Vitamin

sectional

observation

al study

al.,

patients vitamin D, severity D, ina

inammat and acut matory

ory marke e exacer marker

rs, T lymp bation s, and T

2025

[23]

hocytes risk

-cell pa

rameter

s were

correlat

ed with

severity

and exa

cerbatio

n risk

Zhou et China

Prospective COPD Vitamin D Risk of Marked

observation patients deciency severe e vitamin

Table 2: Association of vitamin D with lung function and clinical

respiratory outcomes in COPD.

al.,

2025

al study

n=636 categories xacerbat D dec

[24]

ion

iency w

as asso

ciated

Study

Respiratory Respiratory Main

Overall

Interpretat

ion

Outcomes

Assessed

variables/T Respiratory

ools

Finding

with a

greater

likeliho

od of s

evere

Burkes Lung

et al.,

2020

[9]

function FEV1, longitu Lower 25

Negative

(OH)D was association

associated

and exacerbat dinal lung fun

ion outcomes ction change,

prior exacerba

with worse

cross-section

al and longit

udinal lung

function and

increased od

ds of prior e

xacerbations

COPD

exacerb

ations.

tions

Han et USA,

Cross

Commu Serum 25 FEV1 % Higher

n-ity dw (OH) D predicte vitamin

sectional

study

al.,

NHANE

2025

elling ad

ults with

COPD

(n=1384

)

d, FVC D was

% predic associte

ted, air d with

ow obstr better l

uction s ung fun

[25]

July - September 2026

J Gandhara Med Dent Sci

132

Eects of Vitamin D on Respiratory Function and Immune Status for Patients

Jiang et COPD severi Clinical sev Lower vitamin D Negative

al., 2025 ty and acute erity measur was correlated association

[23] exacerbation es, acute ex with greater COP

risk acerbation D severity and hig

Kim

Emphysem a CT- assessed Severe vitamin Negative

et al., severity and emphysema se Deciency wa association

2020

[11]

progression

verity/progres s associated wi

sion

th emphyse ma

progression in

male COPD

patients.

risk

her risk of acute e

xacerbation

Zhou et Severe

Severe vita Patients with mar Negative

al., 2025 exacerbation min D deci ked vitamin D def association

Jorde et Disease severi COPD severit Lower vitamin Negative

[24] ency categor iciency showed a

risk

al.,

[13]

ty, lung functi y measures, pr D levels were association

ion loss, exac ior FEV1 decl linked with gre

erbation prol ine, exacerbati ater disease se

2021

ies, severe

AECOPD

risk

higher likelihood

of experiencing

severe COPD exa

cerbations.

verity, disease

progression,

and exacerbati

on-related bur

den

Han et Pulmonary FEV1%

The relationship Positive

between serum 25 association

(OH)D and lung

al., 2025 function

[25]

predicted,

and airow FVC%

limitation

predicted,

airow

function was non

linear, with a peak

Lokesh Exacerbation History of ac Vitamin D- de Negative

et al.,

2021[15]

status

ute exacerbati cient COPD association

on in previous patients were

obstruction at higher levels of

severity

serum 25(OH)D.

Rus et Severity duri COPD sever Lower vitamin D Negative

year

more likely to

have previous-

year exacerbat

ions than non-

decint COPD

patients.

al.,

ng acute exa ity during

during acute exac association

erbation was asso

2025

[26]

cerbation

AECOPD

ciated with very

severe COPD.

Lee et Respiratory CAT score, Vitamin D

Negative

25(OH)D = 25-hydroxyvitamin D; AECOPD = acute exacerbation of

chronic obstructive pulmonary disease; CAT= COPDAssessmentTest;

COPD = chronic obstructive pulmonary disease; CT = computed

tomography; FEV1 = forced expiratory volume in 1 second; FVC =

forced vital capacity;QoL= quality of life.

al., 2022 symptom

respiratory

symptom

insufciency/d association

eficiency was

associated with

worse respirato

ry symptoms

[17]

burden

assessment

Table 3 presents the immune and inammatory

outcomes reported in the included original studies.

Overall, the evidence suggests that lower vitamin D

levels in patients with COPD are associated with

increased systemic or airway inammation, altered

vitamin D-related signaling, and poorer immune status.

Several studies reported associations between low

vitamin D levels and inammatory markers, including

CRP, IL-6, and IL-1β. One recent study also showed

that vitamin D levels, inammatory markers, and T-

lymphocyte parameters were correlated with COPD

severity and risk of acute exacerbation. However, the

in stable COP

Rafiq et Exacerbation Exacerbation Vitamin D sup No

al.,

[18]

rate pulmonar rate, pulmona plementation signicant

y function, qu ry function tes did not signic overall

2022

ality of life

ting, QoL mea antly reduce

benet

sures

exacerbation

rate overall

and showed no

clear overall

pulmonary fun

ction benit

Low vitamin Negative

D levels were association

associated

Wang et Symptom

al., 2023 severity

CAT score

evidence

remains

limited,

vitamin

[19]

during

AECOPD

supplementation did not show a consistent anti-

inflammatory benet in all COPD patients with vitamin

D deciency.

with high CAT

scores, sugges

ting greater sy

mptom burden

during an acut

e exacerbation.

Table 3: Eects of vitamin D on immune status and

inammatory markers in patients with COPD.

Lakra et Acute exacerb Acute exacerb Vitamin D3 su Positive e

Study

Immune/ina Immune Main immune Over all inter

al.,

2025

[22]

ations, symto ation frequenc pplementation ect of suppl

m burden, em y, CAT score, decreased acut ementation

mmatory

outcomes

assessed

variables/

tools

pretation

-related

nding

ergency visits emergency

visits

e exacerbation

s, improved C

AT score, and

reduced emerg

ency visits in d

ecient patient

COPD airways Altered airwa

showed altered y vitamin D p

local expressio athway

n of vitamin D-

Vitamin D

receptor

(VDR),

Mathysse Airway vitami

n et al., n D pathway

2020 [12] and local imm

une-related bi CYP27B1,

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133

Eects of Vitamin D on Respiratory Function and Immune Status for Patients

Jiang et al., Inammation Serum 25

2025 [23]

Vitamin D

immune-cell (OH)D, ina levels, in

status in CO mmatory mar ammatory

PD severity kers, T-lymp markers, an

hocyte subset and T-lymp

ology

related gen

es, supprtin

g disturbed

vitamin D

signaling

in the airw

ay microen

vironment

CYP24A1

expression

in airway tiss

hocyte para

meters wer

e correlated

with COPD

severity an

d risk of ac

ute exacerb

Jorde et al., Systemic

Serum

Lower seru Negative asso

m vitamin ciation

[13]

2021

inammation 25(OH)D,

in relation to CRP, IL-6 D levels w

vitamin

status

ere associa

ted with hi

gher syste

mic inam

mation and

greater dis

ease severi

ty in COP

D patients.

ation

Rus et al., Inammatory Serum 25

2025 [26]

Lower vita Negative

association

prole during (OH)D, IL-6 min D duri

acute exacerb

ation

ng acute ex

acerbation

was associa

ted with ve

ry severe C

OPD; IL-6

showed we

aker predic

tive value

than vitami

n D

Fu et al.,

[14]

Inammatory Serum vitami Low vitami Negative

signaling and n D, inamm n D status association

vitamin D

status

2021

atory signali was invers

ng markers, ely associat

pulmonary ed with in

VDR-related ammtory si

signaling

gnaling, wh

ile pulmona

ry nuclear

VDR expre

ssion was

reduced in

COPD.

25(OH)D = 25-hydroxyvitamin D; AECOPD = acute exacerbation of

chronic obstructive pulmonary disease; CAT= COPDAssessmentTest;

CRP = C-reactive protein; CYP27B1 = 25-hydroxyvitamin D3-1α-

hydroxylase; CYP24A1 = 24-hydroxylase; IL = interleukin; VDR =

vitamin D receptor.

Overall, two studies were judged to have a low risk of

bias, 12 studies a moderate risk, and 4 a high risk. The

most frequent methodological limitations were residual

confounding, cross-sectional study design, small

sample size, and lack of temporal assessment between

vitamin D status and COPD outcomes.

Rafiq et al., Inammatory Vitamin D Vitamin D No signicant

2022 [18] after supple suppleme supplement overall benet

mentation ntation with ation did

inammatory not demons

marker asses trate a clear

sment

overall anti

-inammat

ory or clini

cal benet

across the

full vitamin

D-decient

COPD coh

ort

Table 4: Quality appraisal of the included original studies

Author Study

(year) design

Burkes et Observatio JBI Cohort Residual confou Moderate

Appraisal Main sources Summary

tool of bias risk of bias

al., 2020 nal cohort Checklist

[9] analysis

nding, baseline-

only vitamin D

measurement,

observational

design

Wang et al., Inammatory Serum vitam Lower vita Negative

min D level

s and highe

r IL-1β wer

e associated

with greater

symptom b

urden in A

2023 [19]

status during in D, IL-1β,

acute exacer CAT score

bation

association

Köktürk Cross-sect JBI Analytic Single-center

Moderate

et al.,

ional obser al Cross-Sec hospitalized sam

2020 [10] vational

study

tional Check ple, no temporal

list

relationship, pos

sible selection

bias

Kim et al Longitudi JBI Chohort Male-only popul Moderate

ECOPD, su

., 2020

[11]

nal observ Checklist

ational stu

ation, residual co

nounding, possib

le follow-up bias

possible

gdeting a li

nk between

deficiency

and inam

matory acti

vity.

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J Gandhara Med Dent Sci

134

Eects of Vitamin D on Respiratory Function and Immune Status for Patients

Mathysse Translatio JBI Analytica Selected airway High

Zhou et Prospectiv JBI cohort

al., 2025 e observati Checklist

Observational

design, residual

confounding, vit

amin D decienc

y categories may

vary.

Moderate

n et al.,

nal observ l Cross-Secti tissue sample, li

2020 [12] ational

study

lonal Checkli mited generaliza

[24]

onal study

bility, small mec

hanistic sample

Jorde et Cohort

al., 2021 study

[13]

JBI Cohort Small sample

Moderate

size, residual

Checklist

Han et

Cross -

JBI Analytica Secondary popul Moderate

confounding,

single-time

al., 2025 sectional l Cross -

ation dataset, no

temporality,

possible

unmeasured

confounders

[25]

study

Sectional

Checklist

vitamin

assessment

Fu et al., Observatio JBI Analytic Cross-sectional Moderate

2021 [14] nal study al Cross -

Sectional

design, uncertain

control of confou

nders, of possible

reverse causation

Rus et al., Observatio JBI Analytica Acute exacaerba High

2025 [26] nal study l Cross -

Sextional

tion sample, sing

le-center design,

modest sample

size

Checklist

Lokesh et Case-

al., 2021 control

JBI Case - Selection bias, Moderate

Control

Checklist

comparability of

cases and control

s, possible uncon

trolled conoundi

Overall, 2 studies were judged to have low risk of bias, 12 to have

moderate risk of bias, and 4 to have high risk of bias. The most

frequent methodological limitations were residual confounding,

cross-sectional design, small sample size, and lack of temporal

[15]

study

assessment between vitamin

status and COPD outcomes.

Calle Rub Cross -

JBI Analytica Selected high - Moderate

io et al., sectional l Cross -

risk outpatient

population, no

temporality,

possible

2022 [16] study

Sectional

Checklist

DISCUSSION

The present systematic review found a consistent

association between low vitamin D status and poorer

respiratory health in patients with COPD, including

reduced lung function, greater symptom burden, higher

exacerbation risk, and less favorable inammatory

proles. This pattern is supported by recent studies

showing that vitamin D deciency is common among

COPD patients and may be linked with clinical decline,

reduced quality of life, and increased disease burden.

Sun et al. and Fekete et al. also reported that vitamin D

deciency is frequently observed in COPD, although its

causal role remains dicult to conrm, as most

available studies are observational.^27,28Regarding

respiratory outcomes, this review found that lower 25-

hydroxyvitamin D [25(OH)D] levels were generally

associated with poorer FEV1, more severe respiratory

symptoms, emphysema progression, and greater

exacerbation burden. However, the results of

supplementation trials were mixed. The Cochrane

review published in 2024 reported that vitamin D

supplementation had little or no overall eect on

moderate or severe COPD exacerbations, lung function,

mortality, or quality of life in the general COPD

population.⁴Similarly, Hua et al. reported no signicant

reduction in exacerbations or improvement in FEV1 or

FEV1/FVC among vitamin D-decient COPD

patients.²⁹In contrast, Wang et al. found that

supplementation improved pulmonary function and

quality-of-life outcomes.⁶The Lung VITAL trial by

Gold et al. also found no reduction in COPD

exacerbations or improvement in lung function among

adults who were not selected based on vitamin D

deciency.³⁰These ndings suggest that vitamin D

measurement

variation

Lee et al., Cross -

JBI Analytica Cross-sectional Moderate

2022 [17] sectional l Cross -

design, symptom

- based outcome

assessment, resid

ual confounding

study

Sectional

Checklist

Raq et Randomiz Cochrane Ro Minor concerns Low

al., 2022 ed controll B 2 Tool

[18] ed trail

regarding

subgroup respons

iveness and repor

ting of some seco

ndary outcomes

Wang et Cross -

JBI AnalyticaSmall sample

High

al., 2023 sectional l Cross -

size, acute

[19]

study

Sectional

Checklist

exacerbation

setting, limited

adjustment for

confounders

Kola et

Prospecti JBI Analytica Single-center

Moderate

al., 2024 ve cross- l Cross -

sample, modest

sample size, no

casual inference

possible

m [20]

sectional Checklist

study

Jiang et al Cohort

JBI Cohort Secondary databa Moderate

2024 [21] analysis Checklist

se analysis, resid

ual confounding,

nonlinear modeli

ng assumptions

Lakra et Randomiz Cochrane Ro Limited reporting Moderate

al., 2025 ed controll B Tool

[22] ed trail

of allocation con

ealment/blinding,

concealment/

single-center

study

Jiang et Single

al., 2025 cross-

JBI Analytica

l Cross -

Moderate

[23]

sectional Sectional

study

Checklist

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Eects of Vitamin D on Respiratory Function and Immune Status for Patients

supplementation may not benet all COPD patients

separate the independent eect of a single nutrient.

Reviews by Fekete et al., Simon et al., and others

support the need to interpret vitamin D ndings within

equally and that its eect may depend on baseline

vitamin D deciency, disease phenotype, symptom

severity, and the supplementation protocol. The

immune and inammatory ndings of this review are

biologically plausible and are supported by previous

literature. In the included studies, low vitamin D levels

were associated with higher CRP, IL-6, and IL-1β

levels, altered airway vitamin D signaling, and

unfavorable T-lymphocyte proles. Valle et al.

reported that vitamin D deciency in COPD may

broader

nutritional

and

phenotype-based

framework.^28,34,35Overall, the current evidence

supports screening and correcting vitamin D deciency

in high-risk COPD patients, while further well-

designed, stratied randomized trials are needed to

identify the subgroups most likely to benet.

CONCLUSIONS

contribute

mitochondrial dysfunction, and muscle impairment,

while Sun et al. highlighted the possible

inammation,

oxidative

stress,

Vitamin D deciency appears to be an important factor

associated with adverse outcomes in chronic

obstructive pulmonary disease. The ndings of this

systematic review show that low vitamin D levels are

generally linked with poorer respiratory function,

increased exacerbation risk, and altered immune-

inflammatory status. However, intervention studies

have reported inconsistent results, and current evidence

does not support universal vitamin D supplementation

for all COPD patients. Assessment and correction of

vitamin D deciency may be useful in selected high-

risk or decient COPD patients as part of

comprehensive clinical care. Future research should

focus on adequately powered, well-stratied clinical

trials to clarify the therapeutic value of vitamin D in

specic COPD phenotypes and deciency states.

immunomodulatory role of vitamin D.^27,31Anitua et al.

reported that vitamin D supplementation reduced the

overall rate of respiratory infections, particularly when

given daily, and Jollie et al. also found a small but

signicant reduction in acute respiratory infections in

their 2021 meta-analysis.^3,8However, the updated 2025

meta-analysis by Jollie et al. did not show a

statistically signicant reduction in acute respiratory

infections in the overall population.³²Similarly, Shah et

al. reported that the protective eect against respiratory

tract infection was more evident in selected populations

rather than in all healthy adults.³³This indicates that the

immune-related benet of vitamin D may be present but

is likely modest and dependent on patient

characteristics. A possible explanation for the variation

across studies is that vitamin D may act more as a

LIMITATIONS

marker of clinical vulnerability and

targeted

This review has some limitations. Most of the included

studies were observational, limiting causal inference.

There was considerable heterogeneity in study design,

supportive treatment rather than as a universal therapy

for COPD. Previous reviews have shown that the eect

of vitamin D may vary according to baseline vitamin D

concentration, dose, duration of supplementation,

clinical setting, and whether the patient is stable or

experiencing an exacerbation. The benet appears more

likely in patients with marked baseline deciency or a

high risk of exacerbation.⁷The 2024 consensus

statement by Giustina et al. and the Endocrine Society

evidence review by Shah et al. also support a more

individualized approach to vitamin D testing and

replacement, rather than routine supplementation in all

patients without assessment.^5,33These ndings should

be interpreted in light of the limitations of the available

evidence. Most studies included in this review were

observational, and several were cross-sectional with

moderate risk of bias. Therefore, low vitamin D status

may reect reduced outdoor activity, malnutrition,

chronic inammation, frailty, or more severe COPD,

rather than being an independent cause of worse

outcomes. Recent nutritional reviews in COPD have

also emphasized that systemic inammation, poor

dietary intake, muscle wasting, and micronutrient

deciencies often coexist, making it dicult to

population characteristics, vitamin

assessment

methods, supplementation protocols, and reported

outcomes. Several studies also had a moderate to high

risk of bias due to residual confounding, small sample

size, single-center design, and lack of temporal

assessment. In addition, this review included studies

published only between 2020 and 2025. Because of

methodological and clinical heterogeneity across

studies, a meta-analysis was not performed. Therefore,

the ndings should be interpreted with caution.

CONFLICT OF INTEREST: None

FUNDING SOURCES: None

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AUTHORS CONTRIBUTORS

pulmonary

disease.

Nutrients.

2025;17(7):1149.

Sikandar Ali khan - Concept & Design; Data Acquisition;

Data Analysis/Interpretation; Drafting Manuscript; Critical

Revision; Final Approval

https://doi.org/10.3390/nu17071149 (PMID pending)

35. Onur T, et al. Evaluation of micronutrients in stable COPD

patients. Asia Pac

Clin Nutr. 2025;34(5):724-9.

Hina

Hakeem

Concept

Design;

Data

https://doi.org/10.6133/apjcn.202510_34(5).0002

Analysis/Interpretation;

Drafting Manuscript; Critical

Revision; Supervision; Final Approval

Farzana Salman - Concept & Design; Data Acquisition; Data

Analysis/Interpretation;

Revision; Final Approval

Drafting Manuscript; Critical

Shamaila Wadud - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Final Approval

Sara Yar Khan - Concept & Design; Data Acquisition; Data

Analysis/Interpretation; Drafting Manuscript; Final Approval

The authors accept responsibility for all aspects of the work

and will ensure that any concerns regarding the accuracy or

integrity of any part are properly investigated and resolved.

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