The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Oral L-Carnitine Supplementation Increases Trimethylamine-N-oxide but Reduces Markers of Vascular Injury in Hemodialysis Patients
Abstract
OBJECTIVES: Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue. METHODS: Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured. RESULTS: Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043). CONCLUSIONS: This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Supplementation with L-carnitine seems to improve some features of CVD [68] although it raises plasma TMAO and TMA levels [69]”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [69]
In the citing paper
“Although oral supplementation of L-carnitine was associated with increased plasma TMAO concentrations, it decreased vascular injury markers and oxidative stress markers in hemodialysis patients (43).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [43]
Citations
Cites
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,400
Ridker, P. M., Hennekens, C. H., Roitman-Johnson, B., Stampfer, M. J., & Allen, J. (1998) · The Lancet · doi:10.1016/s0140-6736(97)09032-6 · Cited by 1,229
A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection
Suzuki, H. I., Kurihara, Y., Takeya, M., Kamada, N., Kataoka, M., Jishage, K., Ueda, O., Sakaguchi, H., Higashi, T., Suzuki, T., et al. (1997) · Nature · doi:10.1038/386292a0 · Cited by 1,226
Self-citationNakashima, Y., Raines, E. W., Plump, A. S., Breslow, J. L., & Ross, R. (1998) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.18.5.842 · Cited by 917
ICAM-1 signaling in endothelial cells
Lawson, C., & Wolf, S. (2009) · Pharmacological Reports · doi:10.1016/s1734-1140(09)70004-0 · Cited by 685
Expression of intercellular adhesion molecule-1 in atherosclerotic plaques.
Poston, R. N., Haskard, D. O., Coucher, J., Gall, N. P., & Johnson-Tidey, R. R. (1992) · PubMed Central · Cited by 583
Soluble P-Selectin and the Risk of Future Cardiovascular Events
Ridker, P. M., Buring, J. E., & Rifai, N. (2001) · Circulation · doi:10.1161/01.cir.103.4.491 · Cited by 564
Collins, R. G., Velji, R., Guevara, J., Hicks, J. M., Chan, L., & Beaudet, A. L. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.1.189 · Cited by 507
Flagged first, then by citations
Research works printed but not linked: 3
- Ascunce, 2013, Tex Heart Inst J, 40, 104
- Preiss, 2007, 61, 697
- Poston, 1992, Am J Pathol, 140, 665
Cited by
Sorted by citations
Janeiro, M., Ramírez, M., Milagro, F., Martínez, J., & Solas, M. (2018) · Nutrients · doi:10.3390/nu10101398 · Cited by 631
Intestinal Microbiota in Cardiovascular Health and Disease
Tang, W. H. W., Bäckhed, F., Landmesser, U., & Hazen, S. L. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.03.024 · Cited by 524
Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease
Zeisel, S. H., & Warrier, M. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064732 · Cited by 475
Fennema, D., Phillips, I. R., & Shephard, E. A. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.070615 · Cited by 355
TMAO: A small molecule of great expectations
Ufnal, M., Żądło‐Dobrowolska, A., & Ostaszewski, R. (2015) · Nutrition · doi:10.1016/j.nut.2015.05.006 · Cited by 327
Metadata
- Authors
- Fukami, K., Yamagishi, S.-I., Sakai, K., Kaida, Y., Yokoro, M., Ueda, S., Wada, Y., Takeuchi, M., Shimizu, M., Yamazaki, H., & Okuda, S.
- Affiliations
- Kurume University (JP)
- Kanazawa Medical University (JP)
- Showa Pharmaceutical University (JP)
- Corresponding author
- Fukami, Kei
- Sakai, Kazuko
- Kaida, Yusuke
- Yokoro, Miyuki
- Ueda, Seiji
- Okuda, Seiya
- ORCID
- Venue
- Journal of Cardiovascular Pharmacology
- Published
- 2015-03
- Volume
- 65
- Issue
- 3
- Pages
- 289-295
- ISSN
- 0160-2446 (ISSN-L)
- OpenAlex
- W2328568033
- Cited by
- 84
- References
- 33
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 10 · 2020: 14 · 2019: 11 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 3
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26860487)
- Topics
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- carnitine supplementation, trimethylamine N-oxide, trimethylamine, hemodialysis, carnitine deficiency, vascular injury, advanced glycation end products, oxidative stress, soluble ICAM-1, soluble VCAM-1, malondialdehyde, gut microbiota, atherosclerosis, vascular protection
- MeSH terms
- Administration, Oral, Aged, Carnitine, Deficiency Diseases, Female, Renal Dialysis, Humans, Japan, Kidney Diseases, Male, Malondialdehyde, Methylamines, Middle Aged, Time Factors, Biomarkers, Case-Control Studies, Treatment Outcome, Glycation End Products, Advanced, Oxidative Stress, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Dietary Supplements, Vascular System Injuries
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
