Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults
- PMID: 9799203
- DOI: 10.1161/01.cir.98.18.1848
Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults
Abstract
Background: Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults.
Methods and results: Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7. 9+/-2.0 micromol/L at baseline to 23.1+/-5.4 micromol/L at 4 hours (P<0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12+/-0.09 to 0.06+/-0.09 mm (P<0. 05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration.
Conclusions: Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.
Similar articles
-
Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy.Circulation. 1999 Mar 9;99(9):1156-60. doi: 10.1161/01.cir.99.9.1156. Circulation. 1999. PMID: 10069782 Clinical Trial.
-
Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia.Metabolism. 2005 Mar;54(3):351-60. doi: 10.1016/j.metabol.2004.09.015. Metabolism. 2005. PMID: 15736113 Clinical Trial.
-
Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine.Am J Cardiol. 2001 Aug 1;88(3):285-90. doi: 10.1016/s0002-9149(01)01642-3. Am J Cardiol. 2001. PMID: 11472709 Clinical Trial.
-
Homocysteine and endothelial function in human studies.Semin Vasc Med. 2005 May;5(2):172-82. doi: 10.1055/s-2005-872402. Semin Vasc Med. 2005. PMID: 16047269 Review.
-
Hyperhomocysteinemia and cardiovascular risk in postmenopausal women: the role of folate supplementation.Clin Chem Lab Med. 2007;45(2):130-5. doi: 10.1515/CCLM.2007.067. Clin Chem Lab Med. 2007. PMID: 17311496 Review.
Cited by
-
Notorious oxide.Anesthesiology. 2012 Jul;117(1):3-5. doi: 10.1097/ALN.0b013e318259a8e8. Anesthesiology. 2012. PMID: 22569133 Free PMC article. No abstract available.
-
Effect of methionine loading on pulse wave analysis in elderly volunteers.Postgrad Med J. 2006 Aug;82(970):524-7. doi: 10.1136/pgmj.2005.044610. Postgrad Med J. 2006. PMID: 16891444 Free PMC article. Clinical Trial.
-
Hyperhomocysteinemia and endothelial function in young subjects: effects of vitamin supplementation.Clin Cardiol. 2002 Nov;25(11):495-501. doi: 10.1002/clc.4960251105. Clin Cardiol. 2002. PMID: 12430779 Free PMC article. Clinical Trial.
-
Hyperhomocysteinemia and thrombosis.Lipids. 2001;36 Suppl:S13-26. doi: 10.1007/s11745-001-0677-9. Lipids. 2001. PMID: 11837987 Review.
-
Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid.J Orthop Res. 2011 Oct;29(10):1511-6. doi: 10.1002/jor.21415. Epub 2011 Apr 5. J Orthop Res. 2011. PMID: 21469179 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources