l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study
Abstract Background l-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety of l-carnitine, we assessed how genetically different levels of l-carnitine are associated with CVD risk and i...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-09-01
|
| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-022-02477-z |
| _version_ | 1828143971104194560 |
|---|---|
| author | Jie V. Zhao Stephen Burgess Bohan Fan C. Mary Schooling |
| author_facet | Jie V. Zhao Stephen Burgess Bohan Fan C. Mary Schooling |
| author_sort | Jie V. Zhao |
| collection | DOAJ |
| description | Abstract Background l-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety of l-carnitine, we assessed how genetically different levels of l-carnitine are associated with CVD risk and its risk factors. Given higher CVD incidence and l-carnitine in men, we also examined sex-specific associations. Methods We used Mendelian randomization to obtain unconfounded estimates. Specifically, we used genetic variants to predict l-carnitine, and obtained their associations with coronary artery disease (CAD), ischemic stroke, heart failure, and atrial fibrillation, as well as CVD risk factors (type 2 diabetes, glucose, HbA1c, insulin, lipid profile, blood pressure and body mass index) in large consortia and established cohorts, as well as sex-specific association in the UK Biobank. We obtained the Wald estimates (genetic association with CVD and its risk factors divided by the genetic association with l-carnitine) and combined them using inverse variance weighting. In sensitivity analysis, we used different analysis methods robust to pleiotropy and replicated using an l-carnitine isoform, acetyl-carnitine. Results Genetically predicted l-carnitine was nominally associated with higher risk of CAD overall (OR 1.07 per standard deviation (SD) increase in l-carnitine, 95% CI 1.02 to 1.11) and in men (OR 1.09, 95% CI 1.02 to 1.16) but had a null association in women (OR 1.00, 95% CI 0.92 to 1.09). These associations were also robust to different methods and evident for acetyl-carnitine. Conclusions Our findings do not support a beneficial association of l-carnitine with CVD and its risk factors but suggest potential harm. l-carnitine may also exert a sex-specific role in CAD. Consideration of the possible sex disparity and exploration of the underlying pathways would be worthwhile. |
| first_indexed | 2024-04-11T20:08:18Z |
| format | Article |
| id | doaj.art-9e094b85a8d143d5aca676f07fa5c622 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-11T20:08:18Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-9e094b85a8d143d5aca676f07fa5c6222022-12-22T04:05:16ZengBMCBMC Medicine1741-70152022-09-0120111010.1186/s12916-022-02477-zl-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization studyJie V. Zhao0Stephen Burgess1Bohan Fan2C. Mary Schooling3School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong KongMedical Research Council Biostatistics Unit, University of CambridgeSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong KongSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong KongAbstract Background l-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety of l-carnitine, we assessed how genetically different levels of l-carnitine are associated with CVD risk and its risk factors. Given higher CVD incidence and l-carnitine in men, we also examined sex-specific associations. Methods We used Mendelian randomization to obtain unconfounded estimates. Specifically, we used genetic variants to predict l-carnitine, and obtained their associations with coronary artery disease (CAD), ischemic stroke, heart failure, and atrial fibrillation, as well as CVD risk factors (type 2 diabetes, glucose, HbA1c, insulin, lipid profile, blood pressure and body mass index) in large consortia and established cohorts, as well as sex-specific association in the UK Biobank. We obtained the Wald estimates (genetic association with CVD and its risk factors divided by the genetic association with l-carnitine) and combined them using inverse variance weighting. In sensitivity analysis, we used different analysis methods robust to pleiotropy and replicated using an l-carnitine isoform, acetyl-carnitine. Results Genetically predicted l-carnitine was nominally associated with higher risk of CAD overall (OR 1.07 per standard deviation (SD) increase in l-carnitine, 95% CI 1.02 to 1.11) and in men (OR 1.09, 95% CI 1.02 to 1.16) but had a null association in women (OR 1.00, 95% CI 0.92 to 1.09). These associations were also robust to different methods and evident for acetyl-carnitine. Conclusions Our findings do not support a beneficial association of l-carnitine with CVD and its risk factors but suggest potential harm. l-carnitine may also exert a sex-specific role in CAD. Consideration of the possible sex disparity and exploration of the underlying pathways would be worthwhile.https://doi.org/10.1186/s12916-022-02477-zCarnitineMendelian randomizationCardiovascular disease |
| spellingShingle | Jie V. Zhao Stephen Burgess Bohan Fan C. Mary Schooling l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study BMC Medicine Carnitine Mendelian randomization Cardiovascular disease |
| title | l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study |
| title_full | l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study |
| title_fullStr | l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study |
| title_full_unstemmed | l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study |
| title_short | l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study |
| title_sort | l carnitine a friend or foe for cardiovascular disease a mendelian randomization study |
| topic | Carnitine Mendelian randomization Cardiovascular disease |
| url | https://doi.org/10.1186/s12916-022-02477-z |
| work_keys_str_mv | AT jievzhao lcarnitineafriendorfoeforcardiovasculardiseaseamendelianrandomizationstudy AT stephenburgess lcarnitineafriendorfoeforcardiovasculardiseaseamendelianrandomizationstudy AT bohanfan lcarnitineafriendorfoeforcardiovasculardiseaseamendelianrandomizationstudy AT cmaryschooling lcarnitineafriendorfoeforcardiovasculardiseaseamendelianrandomizationstudy |