Display options
Cite
Heianza Y, Ma W, DiDonato JA, et al. Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease. Eur J Nutr. 2021;doi: 10.1007/s00394-021-02713-x.
Heianza, Y., Ma, W., DiDonato, J. A., Sun, Q., Rimm, E. B., Hu, F. B., Rexrode, K. M., Manson, J. E., & Qi, L. (2021). Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease. European journal of nutrition, . https://doi.org/10.1007/s00394-021-02713-x
Heianza, Yoriko, et al. "Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease." European journal of nutrition vol. (2021). doi: https://doi.org/10.1007/s00394-021-02713-x
Heianza Y, Ma W, DiDonato JA, Sun Q, Rimm EB, Hu FB, Rexrode KM, Manson JE, Qi L. Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease. Eur J Nutr. 2021 Nov 19; doi: 10.1007/s00394-021-02713-x. Epub 2021 Nov 19. PMID: 34799774.
Copy Download .nbib Format: NLM
Share it on

Eur J Nutr. 2021 Nov 19; doi: 10.1007/s00394-021-02713-x. Epub 2021 Nov 19.

Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease.

European journal of nutrition

Yoriko Heianza, Wenjie Ma, Joseph A DiDonato, Qi Sun, Eric B Rimm, Frank B Hu, Kathryn M Rexrode, JoAnn E Manson, Lu Qi

Affiliations

  1. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1724, 70112, New Orleans, LA, USA.
  2. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  3. Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  5. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  7. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  8. Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  9. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1724, 70112, New Orleans, LA, USA. [email protected].
  10. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. [email protected].
  11. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. [email protected].

PMID: 34799774 DOI: 10.1007/s00394-021-02713-x

Abstract

PURPOSE: L-Carnitine is abundant in animal source foods, particularly red meat, and circulating L-carnitine may be related to the incidence of coronary heart disease (CHD). We investigated whether long-term changes in plasma L-carnitine over 10 years were associated with the CHD incidence and also examined joint associations of carnitine-rich red meat consumption and L-carnitine changes on the subsequent risk of CHD.

METHODS: This prospective nested case-control study included 772 healthy women at baseline (386 incident CHD cases and 386 healthy controls). Plasma L-carnitine levels were measured both at the first (1989-90) and second blood collections (2000-02). Incident cases of CHD were prospectively followed from the date of the second blood collection through 2016.

RESULTS: Overall, a greater increase in L-carnitine from the first to the second time point was related to a higher risk of CHD, regardless of the initial L-carnitine levels (relative risk: 1.36 (95% CI 0.999, 1.84) per 1-SD increase). The 10-year changes in L-carnitine were positively associated with red meat consumption over time, and women with higher red meat intake (≥ 36 g/day) and with greater increases in L-carnitine had a 1.86 (95% CI 1.13, 3.09) times increased risk of CHD, as compared to those with lower red meat intake and lesser increases in L-carnitine.

CONCLUSION: Long-term increases in L-carnitine levels were associated with the subsequent incidence of CHD, especially among women with higher intake of red meat. Our results suggest the importance of atherogenic L-carnitine changes and dietary intakes over time in the prevention of CHD.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

Keywords: Coronary heart disease; Diet; Gut microbiota-related metabolite; L-Carnitine; Risk; Trimethylamine N-oxide

References

  1. Jie Z, Xia H, Zhong SL et al (2017) The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun 8:845 - PubMed
  2. Zununi Vahed S, Barzegari A, Zuluaga M, Letourneur D, Pavon-Djavid G (2018) Myocardial infarction and gut microbiota: An incidental connection. Pharmacol Res 129:308–317 - PubMed
  3. Zhu Q, Gao R, Zhang Y et al (2018) Dysbiosis signatures of gut microbiota in coronary artery disease. Physiol Genomics 50:893–903 - PubMed
  4. Cui L, Zhao T, Hu H, Zhang W, Hua X (2017) Association study of gut flora in coronary heart disease through high-throughput sequencing. Biomed Res Int 2017:3796359 - PubMed
  5. Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L (2017) Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies. J Am Heart Assoc 6 - PubMed
  6. Qi J, You T, Li J et al (2018) Circulating trimethylamine N-oxide and the risk of cardiovascular diseases: a systematic review and meta-analysis of 11 prospective cohort studies. J Cell Mol Med 22:185–194 - PubMed
  7. Schiattarella GG, Sannino A, Toscano E et al (2017) Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis. Eur Heart J 38:2948–2956 - PubMed
  8. Wang Z, Klipfell E, Bennett BJ et al (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63 - PubMed
  9. Koeth RA, Wang Z, Levison BS et al (2013) Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19:576–585 - PubMed
  10. Bennett BJ, de Aguiar Vallim TQ, Wang Z et al (2013) Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab 17:49–60 - PubMed
  11. Schugar RC, Brown JM (2015) Emerging roles of flavin monooxygenase 3 in cholesterol metabolism and atherosclerosis. Curr Opin Lipidol 26:426–431 - PubMed
  12. Heianza Y, Ma W, DiDonato JA et al (2020) Long-term changes in gut microbial metabolite trimethylamine N-Oxide and coronary heart disease risk. J Am Coll Cardiol 75:763–772 - PubMed
  13. Koeth RA, Lam-Galvez BR, Kirsop J et al (2019) l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J Clin Invest 129:373–387 - PubMed
  14. Zhu Y, Jameson E, Crosatti M et al (2014) Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc Natl Acad Sci U S A 111:4268–4273 - PubMed
  15. Motika MS, Zhang J, Cashman JR (2007) Flavin-containing monooxygenase 3 and human disease. Expert Opin Drug Metab Toxicol 3:831–845 - PubMed
  16. Sinha A, Ma Y, Scherzer R et al (2019) Carnitine Is Associated With Atherosclerotic Risk and Myocardial Infarction in HIV -Infected Adults. J Am Heart Assoc 8:e011037 - PubMed
  17. Wang Z, Bergeron N, Levison BS et al (2019) Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J 40:583–594 - PubMed
  18. Bao Y, Bertoia ML, Lenart EB et al (2016) Origin, methods, and evolution of the three nurses’ health studies. Am J Public Health 106:1573–1581 - PubMed
  19. Heianza Y, Qi L (2020) Reply: TMAO changes and coronary heart disease risk: potential impact and study considerations. J Am Coll Cardiol 75:3102–3104 - PubMed
  20. Mendis S, Thygesen K, Kuulasmaa K et al (2011) World Health Organization definition of myocardial infarction: 2008–09 revision. Int J Epidemiol 40:139–146 - PubMed
  21. Stampfer MJ, Willett WC, Speizer FE et al (1984) Test of the national death index. Am J Epidemiol 119:837–839 - PubMed
  22. Tang WH, Wang Z, Levison BS et al (2013) Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 368:1575–1584 - PubMed
  23. Hu FB, Rimm E, Smith-Warner SA et al (1999) Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire. Am J Clin Nutr 69:243–249 - PubMed
  24. Willett WC, Sampson L, Stampfer MJ et al (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122:51–65 - PubMed
  25. Yuan C, Spiegelman D, Rimm EB et al (2017) Validity of a dietary questionnaire assessed by comparison with multiple weighed dietary records or 24-hour recalls. Am J Epidemiol 185:570–584 - PubMed
  26. Salvini S, Hunter DJ, Sampson L et al (1989) Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 18:858–867 - PubMed
  27. Li XS, Wang Z, Cajka T et al (2018) Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight 3 - PubMed
  28. Bernstein AM, Sun Q, Hu FB, Stampfer MJ, Manson JE, Willett WC (2010) Major dietary protein sources and risk of coronary heart disease in women. Circulation 122:876–883 - PubMed
  29. Pan A, Sun Q, Bernstein AM et al (2012) Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med 172:555–563 - PubMed
  30. Rimm EB, Stampfer MJ, Colditz GA, Chute CG, Litin LB, Willett WC (1990) Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1:466–473 - PubMed
  31. Colditz GA, Martin P, Stampfer MJ et al (1986) Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am J Epidemiol 123:894–900 - PubMed
  32. Manson JE, Colditz GA, Stampfer MJ et al (1991) A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 151:1141–1147 - PubMed
  33. Chiuve SE, Fung TT, Rimm EB et al (2012) Alternative dietary indices both strongly predict risk of chronic disease. J Nutr 142:1009–1018 - PubMed
  34. Qi L, Ma W, Heianza Y et al (2017) Independent and synergistic associations of biomarkers of vitamin d status with risk of coronary heart disease. Arterioscler Thromb Vasc Biol 37:2204–2212 - PubMed
  35. Durrleman S, Simon R (1989) Flexible regression models with cubic splines. Stat Med 8:551–561 - PubMed
  36. Ley SH, Sun Q, Willett WC et al (2014) Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women. Am J Clin Nutr 99:352–360 - PubMed
  37. Skagen K, Troseid M, Ueland T et al (2016) The Carnitine-butyrobetaine-trimethylamine-N-oxide pathway and its association with cardiovascular mortality in patients with carotid atherosclerosis. Atherosclerosis 247:64–69 - PubMed
  38. Heianza Y, Sun D, Li X et al (2019) Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial. Gut 68:263–270 - PubMed
  39. Heianza Y, Sun D, Smith SR, Bray GA, Sacks FM, Qi L (2018) Changes in gut microbiota-related metabolites and long-term successful weight loss in response to weight-loss diets: the pounds lost trial. Diabetes Care 41:413–419 - PubMed
  40. Gao X, Tian Y, Randell E, Zhou H, Sun G (2019) Unfavorable associations between serum trimethylamine N-Oxide and L-Carnitine levels with components of metabolic syndrome in the newfoundland population. Front Endocrinol (Lausanne) 10:168 - PubMed
  41. Wu WK, Chen CC, Liu PY et al (2019) Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice. Gut 68:1439–1449 - PubMed
  42. He K, Song Y, Daviglus ML et al (2004) Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation 109:2705–2711 - PubMed
  43. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines - PubMed
  44. Johnston BC, Zeraatkar D, Han MA et al (2019) Unprocessed red meat and processed meat consumption: dietary guideline recommendations from the nutritional recommendations (NutriRECS) consortium. Ann Intern Med 171:756–764 - PubMed

Publication Types

Grant support