Introduction: There were limited observation studies on the association between tea intake and amyotrophic lateral sclerosis (ALS) with inconsistent results. This study aimed to determine the potential relationship between tea intake and ALS by a two-sample Mendelian randomization (MR) analysis. Methods: We identified 41 independent SNPs strongly associated with tea intake from 448,060 participants of European ancestry in the UK Biobank. Summary statistics associated with ALS were also obtained from the UK Biobank including 20,806 cases and 59,804 controls. The study used MR analysis to assess the potential effect of tea consumption on ALS, and several methods such as sensitivity analyses and MR-pleiotropy residual sum and outlier method were performed to further test the robustness of our findings. Results: The F statistic was more than 10 in each SNP, which meets the first assumption for the MR study. Using the inverse variance weighted MR analysis as the primary method, we found that a one standard deviation increase in tea consumption was associated with a 14% lower risk of ALS (OR = 0.86, 95% CI = 0.74–0.99, p < 0.05). Sensitivity analyses detected no potential pleiotropy and directional heterogeneity. Conclusion: Our MR study supported the potential relationship between tea intake and ALS risk, suggesting the potential advantages of tea intake for preventing ALS. Future clinical trials and research are needed to further validate the results and elucidate possible mechanisms.

1.
van Es
MA
,
Hardiman
O
,
Chio
A
,
Al-Chalabi
A
,
Pasterkamp
RJ
,
Veldink
JH
, et al
.
Amyotrophic lateral sclerosis
.
Lancet
.
2017
;
390
(
10107
):
2084
98
.
2.
Longinetti
E
,
Fang
F
.
Epidemiology of amyotrophic lateral sclerosis: an update of recent literature
.
Curr Opin Neurol
.
2019
;
32
(
5
):
771
6
.
3.
Wolfson
C
,
Gauvin
DE
,
Ishola
F
,
Oskoui
M
.
Global prevalence and incidence of amyotrophic lateral sclerosis: a systematic review
.
Neurology
.
2023
;
101
(
6
):
e613
23
.
4.
Brenner
D
,
Freischmidt
A
.
Update on genetics of amyotrophic lateral sclerosis
.
Curr Opin Neurol
.
2022
;
35
(
5
):
672
7
.
5.
Goutman
SA
,
Hardiman
O
,
Al-Chalabi
A
,
Chio
A
,
Savelieff
MG
,
Kiernan
MC
, et al
.
Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis
.
Lancet Neurol
.
2022
;
21
(
5
):
465
79
.
6.
Hobson
EV
,
McDermott
CJ
.
Supportive and symptomatic management of amyotrophic lateral sclerosis
.
Nat Rev Neurol
.
2016
;
12
(
9
):
526
38
.
7.
Kim
TL
,
Jeong
GH
,
Yang
JW
,
Lee
KH
,
Kronbichler
A
,
van der Vliet
HJ
, et al
.
Tea consumption and risk of cancer: an umbrella review and meta-analysis of observational studies
.
Adv Nutr
.
2020
;
11
(
6
):
1437
52
.
8.
Brimson
JM
,
Prasanth
MI
,
Kumaree
KK
,
Thitilertdecha
P
,
Malar
DS
,
Tencomnao
T
, et al
.
Tea plant (camellia sinensis): a current update on use in diabetes, obesity, and cardiovascular disease
.
Nutrients
.
2022
;
15
(
1
):
37
.
9.
Musial
C
,
Kuban-Jankowska
A
,
Gorska-Ponikowska
M
.
Beneficial properties of green tea catechins
.
Int J Mol Sci
.
2020
;
21
(
5
):
1744
.
10.
Prasanth
MI
,
Sivamaruthi
BS
,
Chaiyasut
C
,
Tencomnao
T
.
A review of the role of green tea (camellia sinensis) in antiphotoaging, stress resistance, neuroprotection, and autophagy
.
Nutrients
.
2019
;
11
(
2
):
474
.
11.
Kakutani
S
,
Watanabe
H
,
Murayama
N
.
Green tea intake and risks for dementia, Alzheimer’s disease, mild cognitive impairment, and cognitive impairment: a systematic review
.
Nutrients
.
2019
;
11
(
5
):
1165
.
12.
Malar
DS
,
Prasanth
MI
,
Brimson
JM
,
Sharika
R
,
Sivamaruthi
BS
,
Chaiyasut
C
, et al
.
Neuroprotective properties of green tea (camellia sinensis) in Parkinson’s disease: a review
.
Molecules
.
2020
;
25
(
17
):
3926
.
13.
Pupillo
E
,
Bianchi
E
,
Chio
A
,
Casale
F
,
Zecca
C
,
Tortelli
R
, et al
.
Amyotrophic lateral sclerosis and food intake
.
Amyotroph Lateral Scler Frontotemporal Degener
.
2018
;
19
(
3–4
):
267
74
.
14.
Fondell
E
,
O'Reilly
EI
,
Fitzgerald
KC
,
Falcone
GJ
,
Kolonel
LN
,
Park
Y
, et al
.
Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: results from five cohort studies
.
Amyotroph Lateral Scler Frontotemporal Degener
.
2015
;
16
(
5–6
):
366
71
.
15.
Haycock
PC
,
Burgess
S
,
Wade
KH
,
Bowden
J
,
Relton
C
,
Davey Smith
G
.
Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies
.
Am J Clin Nutr
.
2016
;
103
(
4
):
965
78
.
16.
Zheng
J
,
Baird
D
,
Borges
MC
,
Bowden
J
,
Hemani
G
,
Haycock
P
, et al
.
Recent developments in mendelian randomization studies
.
Curr Epidemiol Rep
.
2017
;
4
(
4
):
330
45
.
17.
Hingorani
A
,
Humphries
S
.
Nature’s randomised trials
.
Lancet
.
2005
;
366
(
9501
):
1906
8
.
18.
Davey Smith
G
,
Hemani
G
.
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
.
Hum Mol Genet
.
2014
;
23
(
R1
):
R89
98
.
19.
Harshfield
EL
,
Georgakis
MK
,
Malik
R
,
Dichgans
M
,
Markus
HS
.
Modifiable lifestyle factors and risk of stroke: a mendelian randomization analysis
.
Stroke
.
2021
;
52
(
3
):
931
6
.
20.
Yuan
S
,
Gill
D
,
Giovannucci
EL
,
Larsson
SC
.
Obesity, type 2 diabetes, lifestyle factors, and risk of gallstone disease: a mendelian randomization investigation
.
Clin Gastroenterol Hepatol
.
2022
;
20
(
3
):
e529
37
.
21.
Navale
SS
,
Mulugeta
A
,
Zhou
A
,
Llewellyn
DJ
,
Hypponen
E
.
Vitamin D and brain health: an observational and Mendelian randomization study
.
Am J Clin Nutr
.
2022
;
116
(
2
):
531
40
.
22.
Bycroft
C
,
Freeman
C
,
Petkova
D
,
Band
G
,
Elliott
LT
,
Sharp
K
, et al
.
The UK Biobank resource with deep phenotyping and genomic data
.
Nature
.
2018
;
562
(
7726
):
203
9
.
23.
Nicolas
A
,
Kenna
KP
,
Renton
AE
,
Ticozzi
N
,
Faghri
F
,
Chia
R
, et al
.
Genome-wide analyses identify KIF5A as a novel ALS gene
.
Neuron
.
2018
;
97
(
6
):
1267
88
.
24.
Pierce
BL
,
Ahsan
H
,
Vanderweele
TJ
.
Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants
.
Int J Epidemiol
.
2011
;
40
(
3
):
740
52
.
25.
Cucovici
A
,
Ivashynka
A
,
Fontana
A
,
Russo
S
,
Mazzini
L
,
Mandrioli
J
, et al
.
Coffee and tea consumption impact on amyotrophic lateral sclerosis progression: a multicenter cross-sectional study
.
Front Neurol
.
2021
;
12
:
637939
.
26.
Petimar
J
,
O'Reilly
E
,
Adami
HO
,
van den Brandt
PA
,
Buring
J
,
English
DR
, et al
.
Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies
.
Eur J Neurol
.
2019
;
26
(
3
):
468
75
.
27.
Morozova
N
,
Weisskopf
MG
,
McCullough
ML
,
Munger
KL
,
Calle
EE
,
Thun
MJ
, et al
.
Diet and amyotrophic lateral sclerosis
.
Epidemiology
.
2008
;
19
(
2
):
324
37
.
28.
Chen
SQ
,
Wang
ZS
,
Ma
YX
,
Zhang
W
,
Lu
JL
,
Liang
YR
, et al
.
Neuroprotective effects and mechanisms of tea bioactive components in neurodegenerative diseases
.
Molecules
.
2018
;
23
(
3
):
512
.
29.
Koh
SH
,
Lee
SM
,
Kim
HY
,
Lee
KY
,
Lee
YJ
,
Kim
HT
, et al
.
The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice
.
Neurosci Lett
.
2006
;
395
(
2
):
103
7
.
30.
Xu
Z
,
Chen
S
,
Li
X
,
Luo
G
,
Li
L
,
Le
W
.
Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis
.
Neurochem Res
.
2006
;
31
(
10
):
1263
9
.
31.
Che
F
,
Wang
G
,
Yu
J
,
Wang
X
,
Lu
Y
,
Fu
Q
, et al
.
Effects of epigallocatechin-3-gallate on iron metabolism in spinal cord motor neurons
.
Mol Med Rep
.
2017
;
16
(
3
):
3010
4
.
32.
Zhao
B
,
Zhuang
X
,
Pi
Z
,
Liu
S
,
Liu
Z
,
Song
F
.
Determining the effect of catechins on SOD1 conformation and aggregation by ion mobility mass spectrometry combined with optical spectroscopy
.
J Am Soc Mass Spectrom
.
2018
;
29
(
4
):
734
41
.
33.
Qassim
HM
,
Seyedalipour
B
,
Baziyar
P
,
Ahamady-Asbchin
S
.
Polyphenolic flavonoid compounds act as the inhibitory potential of aggregation process: implications for the prevention and therapeutics against FALS-associated D101G SOD1 mutant
.
Comput Biol Chem
.
2023
;
107
:
107967
.
34.
Srinivasan
E
,
Rajasekaran
R
.
Probing the inhibitory activity of epigallocatechin-gallate on toxic aggregates of mutant (L84F) SOD1 protein through geometry based sampling and steered molecular dynamics
.
J Mol Graph Model
.
2017
;
74
:
288
95
.
35.
Chen
JF
,
Schwarzschild
MA
.
Do caffeine and more selective adenosine A(2A) receptor antagonists protect against dopaminergic neurodegeneration in Parkinson's disease
.
Parkinsonism Relat Disord
.
2020
;
80
(
Suppl 1
):
S45
53
.
36.
Ikram
M
,
Park
TJ
,
Ali
T
,
Kim
MO
.
Antioxidant and neuroprotective effects of caffeine against Alzheimer’s and Parkinson’s disease: insight into the role of nrf-2 and A2AR signaling
.
Antioxidants
.
2020
;
9
(
9
):
902
.
37.
Rei
N
,
Valente
CA
,
Vaz
SH
,
Farinha-Ferreira
M
,
Ribeiro
JA
,
Sebastiao
AM
.
Changes in adenosine receptors and neurotrophic factors in the SOD1G93A mouse model of amyotrophic lateral sclerosis: modulation by chronic caffeine
.
PLoS One
.
2022
;
17
(
12
):
e0272104
.
38.
Potenza
RL
,
Armida
M
,
Ferrante
A
,
Pezzola
A
,
Matteucci
A
,
Puopolo
M
, et al
.
Effects of chronic caffeine intake in a mouse model of amyotrophic lateral sclerosis
.
J Neurosci Res
.
2013
;
91
(
4
):
585
92
.
39.
Sebastiao
AM
,
Rei
N
,
Ribeiro
JA
.
Amyotrophic Lateral Sclerosis (ALS) and adenosine receptors
.
Front Pharmacol
.
2018
;
9
:
267
.
40.
Zwilling
M
,
Theiss
C
,
Matschke
V
.
Caffeine and NAD(+) improve motor neural integrity of dissociated wobbler cells in vitro
.
Antioxidants
.
2020
;
9
(
6
):
460
.
41.
Brothers
HM
,
Marchalant
Y
,
Wenk
GL
.
Caffeine attenuates lipopolysaccharide-induced neuroinflammation
.
Neurosci Lett
.
2010
;
480
(
2
):
97
100
.
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