Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study

Alice Giontella; Roxane de La Harpe; Héléne T. Cronje; Loukas Zagkos; Benjamin Woolf; Susanna C. Larsson; Dipender Gill

doi:10.3390/nu15204422

Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study

Alice Giontella, Roxane de La Harpe, Héléne T. Cronje, Loukas Zagkos, Benjamin Woolf, Susanna C. Larsson, Dipender Gill^*

^*Corresponding author af dette arbejde

Afdeling for Epidemiologi

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

12 Citationer (Scopus)

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Abstract

affeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the CYP1A2 and AHR genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits. Genetic association summary statistics on plasma caffeine levels and caffeine intake were taken from genome-wide association study (GWAS) meta-analyses of 9876 and of >47,000 European ancestry individuals, respectively. Genetically predicted plasma caffeine levels were associated with a decrease in estimated glomerular filtration rate (eGFR) measured using either creatinine or cystatin C. In contrast, genetically predicted caffeine intake was associated with an increase in eGFR and a low risk of chronic kidney disease. The discrepancy is likely attributable to faster metabolizers of caffeine consuming more caffeine-containing beverages to achieve the same pharmacological effect. Further research is needed to distinguish whether the observed effects on kidney function are driven by the harmful effects of higher plasma caffeine levels or the protective effects of greater intake of caffeine-containing beverages, particularly given the widespread use of drinks containing caffeine and the increasing burden of kidney disease.
Keywords: caffeine level; caffeine intake; genetically predicted coffee consumption; causal inference; Mendelian randomization; kidney function; estimated glomerular filtration rate

Originalsprog	Engelsk
Artikelnummer	4422
Tidsskrift	Nutrients
Vol/bind	15
Udgave nummer	20
Antal sider	7
ISSN	2072-6643
DOI	https://doi.org/10.3390/nu15204422
Status	Udgivet - 2023

Bibliografisk note

Funding Information:
D.G. is supported by the British Heart Foundation Centre of Research Excellence (RE/18/4/34215) at Imperial College. S.C.L. receives funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, grant number 20210351), the Swedish Research Council for Health, Working Life and Welfare (Forte, grant number 2018-00123), the Swedish Research Council (Vetenskapsrådet, grant number 2019-00977), and the Swedish Cancer Society (Cancerfonden).

Publisher Copyright:
© 2023 by the authors.

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title = "Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study",

abstract = "Caffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the CYP1A2 and AHR genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits. Genetic association summary statistics on plasma caffeine levels and caffeine intake were taken from genome-wide association study (GWAS) meta-analyses of 9876 and of >47,000 European ancestry individuals, respectively. Genetically predicted plasma caffeine levels were associated with a decrease in estimated glomerular filtration rate (eGFR) measured using either creatinine or cystatin C. In contrast, genetically predicted caffeine intake was associated with an increase in eGFR and a low risk of chronic kidney disease. The discrepancy is likely attributable to faster metabolizers of caffeine consuming more caffeine-containing beverages to achieve the same pharmacological effect. Further research is needed to distinguish whether the observed effects on kidney function are driven by the harmful effects of higher plasma caffeine levels or the protective effects of greater intake of caffeine-containing beverages, particularly given the widespread use of drinks containing caffeine and the increasing burden of kidney disease.",

keywords = "caffeine intake, caffeine level, causal inference, estimated glomerular filtration rate, genetically predicted coffee consumption, kidney function, Mendelian randomization",

author = "Alice Giontella and {de La Harpe}, Roxane and Cronje, {H{\'e}l{\'e}ne T.} and Loukas Zagkos and Benjamin Woolf and Larsson, {Susanna C.} and Dipender Gill",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

doi = "10.3390/nu15204422",

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T1 - Caffeine Intake, Plasma Caffeine Level, and Kidney Function

T2 - A Mendelian Randomization Study

AU - Giontella, Alice

AU - de La Harpe, Roxane

AU - Cronje, Héléne T.

AU - Zagkos, Loukas

AU - Woolf, Benjamin

AU - Larsson, Susanna C.

AU - Gill, Dipender

PY - 2023

Y1 - 2023

N2 - Caffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the CYP1A2 and AHR genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits. Genetic association summary statistics on plasma caffeine levels and caffeine intake were taken from genome-wide association study (GWAS) meta-analyses of 9876 and of >47,000 European ancestry individuals, respectively. Genetically predicted plasma caffeine levels were associated with a decrease in estimated glomerular filtration rate (eGFR) measured using either creatinine or cystatin C. In contrast, genetically predicted caffeine intake was associated with an increase in eGFR and a low risk of chronic kidney disease. The discrepancy is likely attributable to faster metabolizers of caffeine consuming more caffeine-containing beverages to achieve the same pharmacological effect. Further research is needed to distinguish whether the observed effects on kidney function are driven by the harmful effects of higher plasma caffeine levels or the protective effects of greater intake of caffeine-containing beverages, particularly given the widespread use of drinks containing caffeine and the increasing burden of kidney disease.

AB - Caffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the CYP1A2 and AHR genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits. Genetic association summary statistics on plasma caffeine levels and caffeine intake were taken from genome-wide association study (GWAS) meta-analyses of 9876 and of >47,000 European ancestry individuals, respectively. Genetically predicted plasma caffeine levels were associated with a decrease in estimated glomerular filtration rate (eGFR) measured using either creatinine or cystatin C. In contrast, genetically predicted caffeine intake was associated with an increase in eGFR and a low risk of chronic kidney disease. The discrepancy is likely attributable to faster metabolizers of caffeine consuming more caffeine-containing beverages to achieve the same pharmacological effect. Further research is needed to distinguish whether the observed effects on kidney function are driven by the harmful effects of higher plasma caffeine levels or the protective effects of greater intake of caffeine-containing beverages, particularly given the widespread use of drinks containing caffeine and the increasing burden of kidney disease.

KW - caffeine intake

KW - caffeine level

KW - causal inference

KW - estimated glomerular filtration rate

KW - genetically predicted coffee consumption

KW - kidney function

KW - Mendelian randomization

U2 - 10.3390/nu15204422

DO - 10.3390/nu15204422

M3 - Journal article

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SN - 2072-6643

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JO - Nutrients

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