Introduction: Previous studies have indicated a controversy regarding the association between dietary micronutrient concentrations and the risk of allergic diseases. In this study, we employed Mendelian randomization (MR) analysis using data from two samples to investigate the causal relationship between circulating micronutrient concentrations and three allergic diseases. Methods: In this study, we considered 16 circulating micronutrients as exposure variables (beta carotene, calcium, copper, folate, iron, lycopene, magnesium, phosphorus, selenium, vitamin A1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and zinc); and three common allergic diseases (allergic asthma [AA], atopic dermatitis [AD], and allergic rhinitis [AR]) as outcomes. The inverse variance weighted (IVW) method was primarily applied for MR analysis, supplemented by MR-Egger and weighted-median methods to corroborate the IVW results; and sensitivity analysis was conducted to ensure the robustness of the MR assumptions. Results: Our results revealed that an increase in serum phosphorus and zinc concentrations may diminish the risk of AA, while for AD an increase in serum zinc concentration may reduce the risk, but an increase in serum vitamin C concentration may elevate the risk. As for AR, an increase in serum phosphorus and selenium concentrations appeared to be associated with a reduced risk. We did not find evidence for an association between other micronutrients and the risk of allergic diseases. Conclusion: Our study indicates that an increase in serum phosphorus and zinc concentrations may reduce the risk of AA, while an increase in serum zinc concentration may reduce the risk of AD, but an increase in serum vitamin C concentration may elevate the risk of AD. An increase in serum phosphorus and selenium concentrations is associated with a reduced risk of AR. This provides additional support for research on the effects of micronutrients on allergic diseases.

1.
Spergel
JM
.
Epidemiology of atopic dermatitis and atopic march in children
.
Immunol Allergy Clin North Am
.
2010
;
30
(
3
):
269
80
.
2.
Ferreira
MA
,
Vonk
JM
,
Baurecht
H
,
Marenholz
I
,
Tian
C
,
Hoffman
JD
, et al
.
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
.
Nat Genet
.
2017
;
49
(
12
):
1752
7
.
3.
Emberlin
J
,
Detandt
M
,
Gehrig
R
,
Jaeger
S
,
Nolard
N
,
Rantio-Lehtimäki
A
.
Responses in the start of Betula (birch) pollen seasons to recent changes in spring temperatures across Europe
.
Int J Biometeorol
.
2002
;
46
(
4
):
159
70
.
4.
Kim
BJ
,
Seo
JH
,
Jung
YH
,
Kim
HY
,
Kwon
JW
,
Kim
HB
, et al
.
Air pollution interacts with past episodes of bronchiolitis in the development of asthma
.
Allergy
.
2013
;
68
(
4
):
517
23
.
5.
Bisgaard
H
,
Li
N
,
Bonnelykke
K
,
Chawes
BL
,
Skov
T
,
Paludan-Müller
G
, et al
.
Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age
.
J Allergy Clin Immunol
.
2011
;
128
(
3
):
646
52.e1-5
.
6.
Abrahamsson
TR
,
Jakobsson
HE
,
Andersson
AF
,
Björkstén
B
,
Engstrand
L
,
Jenmalm
MC
.
Low diversity of the gut microbiota in infants with atopic eczema
.
J Allergy Clin Immunol
.
2012
;
129
(
2
):
434
40
, 440.e1-2.
7.
Mai
XM
,
Chen
Y
,
Camargo
CA
Jr
,
Langhammer
A
.
Serum 25-hydroxyvitamin D levels and self-reported allergic rhinitis in Norwegian adults - the HUNT Study
.
Allergy
.
2014
;
69
(
4
):
488
93
.
8.
Pike
KC
,
Inskip
HM
,
Robinson
S
,
Lucas
JS
,
Cooper
C
,
Harvey
NC
, et al
.
Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes
.
Thorax
.
2012
;
67
(
11
):
950
6
.
9.
Gale
CR
,
Robinson
SM
,
Harvey
NC
,
Javaid
MK
,
Jiang
B
,
Martyn
CN
, et al
.
Maternal vitamin D status during pregnancy and child outcomes
.
Eur J Clin Nutr
.
2008
;
62
(
1
):
68
77
.
10.
Morales
E
,
Romieu
I
,
Guerra
S
,
Ballester
F
,
Rebagliato
M
,
Vioque
J
, et al
.
Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring
.
Epidemiology
.
2012
;
23
(
1
):
64
71
.
11.
Camargo
CA
Jr
,
Ingham
T
,
Wickens
K
,
Thadhani
R
,
Silvers
KM
,
Epton
MJ
, et al
.
Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma
.
Pediatrics
.
2011
;
127
(
1
):
e180
7
.
12.
Peroni
DG
,
Piacentini
GL
,
Cametti
E
,
Chinellato
I
,
Boner
AL
.
Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children
.
Br J Dermatol
.
2011
;
164
(
5
):
1078
82
.
13.
Samochocki
Z
,
Bogaczewicz
J
,
Jeziorkowska
R
,
Sysa-Jędrzejowska
A
,
Glińska
O
,
Karczmarewicz
E
, et al
.
Vitamin D effects in atopic dermatitis
.
J Am Acad Dermatol
.
2013
;
69
(
2
):
238
44
.
14.
Chiu
YE
,
Havens
PL
,
Siegel
DH
,
Ali
O
,
Wang
T
,
Holland
KE
, et al
.
Serum 25-hydroxyvitamin D concentration does not correlate with atopic dermatitis severity
.
J Am Acad Dermatol
.
2013
;
69
(
1
):
40
6
.
15.
Norizoe
C
,
Akiyama
N
,
Segawa
T
,
Tachimoto
H
,
Mezawa
H
,
Ida
H
, et al
.
Increased food allergy and vitamin D: randomized, double-blind, placebo-controlled trial
.
Pediatr Int
.
2014
;
56
(
1
):
6
12
.
16.
Khan
A
,
Adalsteinsson
J
,
Whitaker-Worth
DL
.
Atopic dermatitis and nutrition
.
Clin Dermatol
.
2022
;
40
(
2
):
135
44
.
17.
Peroni
DG
,
Hufnagl
K
,
Comberiati
P
,
Roth-Walter
F
.
Lack of iron, zinc, and vitamins as a contributor to the etiology of atopic diseases
.
Front Nutr
.
2022
;
9
:
1032481
.
18.
Maazi
H
,
Shirinbak
S
,
Bloksma
N
,
Nawijn
MC
,
van Oosterhout
AJ
.
Iron administration reduces airway hyperreactivity and eosinophilia in a mouse model of allergic asthma
.
Clin Exp Immunol
.
2011
;
166
(
1
):
80
6
.
19.
Ekmekci
OB
,
Donma
O
,
Sardoğan
E
,
Yildirim
N
,
Uysal
O
,
Demirel
H
, et al
.
Iron, nitric oxide, and myeloperoxidase in asthmatic patients
.
Biochemistry
.
2004
;
69
(
4
):
462
7
.
20.
Palma-Carlos
AG
,
Palma-Carlos
ML
,
Costa
AC
.
“Minor” hemoglobinopathies: a risk factor for asthma
.
Eur Ann Allergy Clin Immunol
.
2005
;
37
(
5
):
177
82
.
21.
Wang
J
,
Yin
J
,
Hong
X
,
Liu
R
.
Exposure to heavy metals and allergic outcomes in children: a systematic review and meta-analysis
.
Biol Trace Elem Res
.
2022
;
200
(
11
):
4615
31
.
22.
Stelmach
I
,
Grzelewski
T
,
Bobrowska-Korzeniowska
M
,
Kopka
M
,
Majak
P
,
Jerzynska
J
, et al
.
The role of zinc, copper, plasma glutathione peroxidase enzyme, and vitamins in the development of allergic diseases in early childhood: the Polish mother and child cohort study
.
Allergy Asthma Proc
.
2014
;
35
(
3
):
227
32
.
23.
Wang
T
,
Zhang
HP
,
Zhang
X
,
Liang
ZA
,
Ji
YL
,
Wang
G
.
Is folate status a risk factor for asthma or other allergic diseases
.
Allergy Asthma Immunol Res
.
2015
;
7
(
6
):
538
46
.
24.
Thuesen
BH
,
Husemoen
LL
,
Ovesen
L
,
Jørgensen
T
,
Fenger
M
,
Gilderson
G
, et al
.
Atopy, asthma, and lung function in relation to folate and vitamin B(12) in adults
.
Allergy
.
2010
;
65
(
11
):
1446
54
.
25.
Nurmatov
U
,
Devereux
G
,
Sheikh
A
.
Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis
.
J Allergy Clin Immunol
.
2011
;
127
(
3
):
724
33.e1-30
.
26.
Lawlor
DA
,
Harbord
RM
,
Sterne
JA
,
Timpson
N
,
Davey Smith
G
.
Mendelian randomization: using genes as instruments for making causal inferences in epidemiology
.
Stat Med
.
2008
;
27
(
8
):
1133
63
.
27.
Sanderson
E
,
Davey Smith
G
,
Windmeijer
F
,
Bowden
J
.
An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings
.
Int J Epidemiol
.
2019
;
48
(
3
):
713
27
.
28.
Skrivankova
VW
,
Richmond
RC
,
Woolf
BAR
,
Davies
NM
,
Swanson
SA
,
VanderWeele
TJ
, et al
.
Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration
.
BMJ
.
2021
;
375
:
n2233
.
29.
Ferrucci
L
,
Perry
JR
,
Matteini
A
,
Perola
M
,
Tanaka
T
,
Silander
K
, et al
.
Common variation in the beta-carotene 15,15’-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study
.
Am J Hum Genet
.
2009
;
84
(
2
):
123
33
.
30.
O’Seaghdha
CM
,
Wu
H
,
Yang
Q
,
Kapur
K
,
Guessous
I
,
Zuber
AM
, et al
.
Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations
.
PLoS Genet
.
2013
;
9
(
9
):
e1003796
.
31.
Evans
DM
,
Zhu
G
,
Dy
V
,
Heath
AC
,
Madden
PA
,
Kemp
JP
, et al
.
Genome-wide association study identifies loci affecting blood copper, selenium and zinc
.
Hum Mol Genet
.
2013
;
22
(
19
):
3998
4006
.
32.
Grarup
N
,
Sulem
P
,
Sandholt
CH
,
Thorleifsson
G
,
Ahluwalia
TS
,
Steinthorsdottir
V
, et al
.
Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets
.
PLoS Genet
.
2013
;
9
(
6
):
e1003530
.
33.
Bell
S
,
Rigas
AS
,
Magnusson
MK
,
Ferkingstad
E
,
Allara
E
,
Bjornsdottir
G
, et al
.
A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis
.
Commun Biol
.
2021
;
4
(
1
):
156
.
34.
D’Adamo
CR
,
D’Urso
A
,
Ryan
KA
,
Yerges-Armstrong
LM
,
Semba
RD
,
Steinle
NI
, et al
.
A common variant in the SETD7 gene predicts serum lycopene concentrations
.
Nutrients
.
2016
;
8
(
2
):
82
.
35.
Meyer
TE
,
Verwoert
GC
,
Hwang
SJ
,
Glazer
NL
,
Smith
AV
,
van Rooij
FJ
, et al
.
Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels
.
PLoS Genet
.
2010
;
6
(
8
):
e1001045
.
36.
Kestenbaum
B
,
Glazer
NL
,
Köttgen
A
,
Felix
JF
,
Hwang
SJ
,
Liu
Y
, et al
.
Common genetic variants associate with serum phosphorus concentration
.
J Am Soc Nephrol
.
2010
;
21
(
7
):
1223
32
.
37.
Mondul
AM
,
Yu
K
,
Wheeler
W
,
Zhang
H
,
Weinstein
SJ
,
Major
JM
, et al
.
Genome-wide association study of circulating retinol levels
.
Hum Mol Genet
.
2011
;
20
(
23
):
4724
31
.
38.
Hazra
A
,
Kraft
P
,
Lazarus
R
,
Chen
C
,
Chanock
SJ
,
Jacques
P
, et al
.
Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway
.
Hum Mol Genet
.
2009
;
18
(
23
):
4677
87
.
39.
Zheng
JS
,
Luan
J
,
Sofianopoulou
E
,
Imamura
F
,
Stewart
ID
,
Day
FR
, et al
.
Plasma vitamin C and type 2 diabetes: genome-wide association study and mendelian randomization analysis in European populations
.
Diabetes Care
.
2021
;
44
(
1
):
98
106
.
40.
Jiang
X
,
O’Reilly
PF
,
Aschard
H
,
Hsu
YH
,
Richards
JB
,
Dupuis
J
, et al
.
Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
.
Nat Commun
.
2018
;
9
(
1
):
260
.
41.
Major
JM
,
Yu
K
,
Wheeler
W
,
Zhang
H
,
Cornelis
MC
,
Wright
ME
, et al
.
Genome-wide association study identifies common variants associated with circulating vitamin E levels
.
Hum Mol Genet
.
2011
;
20
(
19
):
3876
83
.
42.
Sanderson
E
,
Glymour
MM
,
Holmes
MV
,
Kang
H
,
Morrison
J
,
Munafò
MR
, et al
.
Mendelian randomization
.
Nat Rev Methods Primers
.
2022
;
2
:
6
.
43.
Burgess
S
,
Thompson
SG
;
CRP CHD Genetics Collaboration
.
Avoiding bias from weak instruments in Mendelian randomization studies
.
Int J Epidemiol
.
2011
;
40
(
3
):
755
64
.
44.
Machiela
MJ
,
Chanock
SJ
.
LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants
.
Bioinformatics
.
2015
;
31
(
21
):
3555
7
.
45.
FinnGen
T
.
FinnGen documentation of R10 release
[cited 2024 4 January 2024]; Available from: https://www.finngen.fi/fi
46.
Wang
S
,
Zhu
H
,
Pan
L
,
Zhang
M
,
Wan
X
,
Xu
H
, et al
.
Systemic inflammatory regulators and risk of acute-on-chronic liver failure: a bidirectional mendelian-randomization study
.
Front Cell Dev Biol
.
2023
;
11
:
1125233
.
47.
Ariaee
N
,
Farid
R
,
Shabestari
F
,
Shabestari
M
,
Jabbari Azad
F
.
Trace elements status in sera of patients with allergic asthma
.
Rep Biochem Mol Biol
.
2016
;
5
(
1
):
20
5
.
48.
Mohamed
NA
,
Rushdy
M
,
Abdel-Rehim
ASM
.
The immunomodulatory role of zinc in asthmatic patients
.
Cytokine
.
2018
;
110
:
301
5
.
49.
Khanbabaee
G
,
Omidian
A
,
Imanzadeh
F
,
Adibeshgh
F
,
Ashayeripanah
M
,
Rezaei
N
.
Serum level of zinc in asthmatic patients: a case-control study
.
Allergol Immunopathol
.
2014
;
42
(
1
):
19
21
.
50.
Andino
D
,
Moy
J
,
Gaynes
BI
.
Serum vitamin A, zinc and visual function in children with moderate to severe persistent asthma
.
J Asthma
.
2019
;
56
(
11
):
1198
203
.
51.
Rajkumar
S
,
Bhat
NK
,
Kumar
V
,
Bolia
R
,
Verma
PK
,
Kumar
M
, et al
.
Association of serum zinc levels and symptom control of asthma in children and adolescents-a prospective observational study
.
Eur J Pediatr
.
2023
;
182
(
1
):
141
7
.
52.
AbdulWahab
A
,
Zeidan
A
,
Avades
T
,
Chandra
P
,
Soliman
A
.
Serum zinc level in asthmatic and non-asthmatic school children
.
Children
.
2018
;
5
(
3
):
42
.
53.
Chiou
YL
.
The supplementation of zinc increased the apoptosis of airway smooth muscle cells by increasing p38 phosphorylation
.
Environ Toxicol Pharmacol
.
2012
;
33
(
1
):
70
7
.
54.
Gray
NA
,
Dhana
A
,
Stein
DJ
,
Khumalo
NP
.
Zinc and atopic dermatitis: a systematic review and meta-analysis
.
J Eur Acad Dermatol Venereol
.
2019
;
33
(
6
):
1042
50
.
55.
Kim
JE
,
Yoo
SR
,
Jeong
MG
,
Ko
JY
,
Ro
YS
.
Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis
.
Acta Derm Venereol
.
2014
;
94
(
5
):
558
62
.
56.
Vaughn
AR
,
Foolad
N
,
Maarouf
M
,
Tran
KA
,
Shi
VY
.
Micronutrients in atopic dermatitis: a systematic review
.
J Altern Complement Med
.
2019
;
25
(
6
):
567
77
.
57.
Shin
J
,
Kim
YJ
,
Kwon
O
,
Kim
NI
,
Cho
Y
.
Associations among plasma vitamin C, epidermal ceramide and clinical severity of atopic dermatitis
.
Nutr Res Pract
.
2016
;
10
(
4
):
398
403
.
58.
Oh
SY
,
Chung
J
,
Kim
MK
,
Kwon
SO
,
Cho
BH
.
Antioxidant nutrient intakes and corresponding biomarkers associated with the risk of atopic dermatitis in young children
.
Eur J Clin Nutr
.
2010
;
64
(
3
):
245
52
.
59.
Miyazaki
J
,
Ikehara
S
,
Tanigawa
K
,
Kimura
T
,
Ueda
K
,
Ozono
K
, et al
.
Prenatal exposure to selenium, mercury, and manganese during pregnancy and allergic diseases in early childhood: the Japan Environment and Children’s study
.
Environ Int
.
2023
;
179
:
108123
.
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