Homocysteine: Difference between revisions

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imported>Robert Badgett
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[[Randomized controlled trial]]s have shown the vitamin supplements can lower the homocysteine level; however, this reduction does not lead to reduced mortality<ref name="pmid17848650">{{cite journal |author=Jamison RL, Hartigan P, Kaufman JS, ''et al'' |title=Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial |journal=JAMA |volume=298 |issue=10 |pages=1163–70 |year=2007 |month=September |pmid=17848650 |doi=10.1001/jama.298.10.1163 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=17848650 |issn=}}</ref><ref name="pmid18714059">{{cite journal |author=Ebbing M, Bleie Ø, Ueland PM, ''et al'' |title=Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial |journal=JAMA |volume=300 |issue=7 |pages=795–804 |year=2008 |month=August |pmid=18714059 |doi=10.1001/jama.300.7.795 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18714059 |issn=}}</ref>, reduced [[coronary heart disease]]<ref name="pmid16531614">{{cite journal |author=Bønaa KH, Njølstad I, Ueland PM, ''et al'' |title=Homocysteine lowering and cardiovascular events after acute myocardial infarction |journal=N. Engl. J. Med. |volume=354 |issue=15 |pages=1578–88 |year=2006 |month=April |pmid=16531614 |doi=10.1056/NEJMoa055227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16531614&promo=ONFLNS19 |issn=}}</ref><ref name="pmid18714059"/> or improved cognition<ref name="pmid16807413">{{cite journal |author=McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM |title=A controlled trial of homocysteine lowering and cognitive performance |journal=N. Engl. J. Med. |volume=354 |issue=26 |pages=2764–72 |year=2006 |month=June |pmid=16807413 |doi=10.1056/NEJMoa054025 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16807413&promo=ONFLNS19 |issn=}}</ref><ref name="pmid18854539">{{cite journal |author=Aisen PS, Schneider LS, Sano M, ''et al'' |title=High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial |journal=JAMA |volume=300 |issue=15 |pages=1774–83 |year=2008 |month=October |pmid=18854539 |doi=10.1001/jama.300.15.1774 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18854539 |issn=}}</ref>
[[Randomized controlled trial]]s have shown the vitamin supplements can lower the homocysteine level; however, this reduction does not lead to reduced mortality<ref name="pmid17848650">{{cite journal |author=Jamison RL, Hartigan P, Kaufman JS, ''et al'' |title=Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial |journal=JAMA |volume=298 |issue=10 |pages=1163–70 |year=2007 |month=September |pmid=17848650 |doi=10.1001/jama.298.10.1163 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=17848650 |issn=}}</ref><ref name="pmid18714059">{{cite journal |author=Ebbing M, Bleie Ø, Ueland PM, ''et al'' |title=Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial |journal=JAMA |volume=300 |issue=7 |pages=795–804 |year=2008 |month=August |pmid=18714059 |doi=10.1001/jama.300.7.795 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18714059 |issn=}}</ref>, reduced [[coronary heart disease]]<ref name="pmid16531614">{{cite journal |author=Bønaa KH, Njølstad I, Ueland PM, ''et al'' |title=Homocysteine lowering and cardiovascular events after acute myocardial infarction |journal=N. Engl. J. Med. |volume=354 |issue=15 |pages=1578–88 |year=2006 |month=April |pmid=16531614 |doi=10.1056/NEJMoa055227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16531614&promo=ONFLNS19 |issn=}}</ref><ref name="pmid18714059"/> or improved cognition<ref name="pmid16807413">{{cite journal |author=McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM |title=A controlled trial of homocysteine lowering and cognitive performance |journal=N. Engl. J. Med. |volume=354 |issue=26 |pages=2764–72 |year=2006 |month=June |pmid=16807413 |doi=10.1056/NEJMoa054025 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16807413&promo=ONFLNS19 |issn=}}</ref><ref name="pmid18854539">{{cite journal |author=Aisen PS, Schneider LS, Sano M, ''et al'' |title=High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial |journal=JAMA |volume=300 |issue=15 |pages=1774–83 |year=2008 |month=October |pmid=18854539 |doi=10.1001/jama.300.15.1774 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18854539 |issn=}}</ref>


A [[meta-analysis]] of these trials by the [[Cochrane Collaboratio]]n concludes that there is no benefit from lowering the homocysteine level.<ref name="pmid19821378">{{cite journal| author=Martí-Carvajal AJ, Solà I, Lathyris D, Salanti G| title=Homocysteine lowering interventions for preventing cardiovascular events. | journal=Cochrane Database Syst Rev | year= 2009 | volume=  | issue= 4 | pages= CD006612 | pmid=19821378  
A [[meta-analysis]] of these trials by the [[Cochrane Collaboration]] concludes that there is no benefit from lowering the homocysteine level.<ref name="pmid19821378">{{cite journal| author=Martí-Carvajal AJ, Solà I, Lathyris D, Salanti G| title=Homocysteine lowering interventions for preventing cardiovascular events. | journal=Cochrane Database Syst Rev | year= 2009 | volume=  | issue= 4 | pages= CD006612 | pmid=19821378  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19821378 | doi=10.1002/14651858.CD006612.pub2 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19821378 | doi=10.1002/14651858.CD006612.pub2 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>


==References==
==References==
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In biochemistry, homocysteine is a "thiol-containing amino acid formed by a demethylation of methionine.[1]

Role in human disease

Homocystinuria

For more information, see: Homocystinuria.

Homocystinuria is an "autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of cystathionine beta-synthase and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall, slender habitus, scoliosis, arachnodactyly, muscle weakness, genu varis, thin blond hair, malar flush, lens dislocations, an increased incidence of mental retardation, and a tendency to develop fibrosis of arteries, frequently complicated by cerebrovascular accidents and myocardial infarction.[2] Homozygous individuals have homocysteine levels that are five times the normal level.[3]

Hyperhomocysteinemia

For more information, see: Hyperhomocysteinemia.

Hyperhomocysteinemia is an "inborn error of methionine metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine beta-synthase and is a risk factor for coronary vascular disease."[4][5]

Methylenetetrahydrofolate reductase deficiency

About 10% of people are homozygous for the single gene mutation (cytosine is replaced by thymidine at base position 677) that reduces the activity of the enzyme methylenetetrahydrofolate reductase (MTHFR).[3][6] These individuals with TT genotype have a 20% increase in serum homocysteine levels and may have increased coronary heart disease.[3][6][7]

Treatment to reduce homocysteine levels

Randomized controlled trials have shown the vitamin supplements can lower the homocysteine level; however, this reduction does not lead to reduced mortality[8][9], reduced coronary heart disease[10][9] or improved cognition[11][12]

A meta-analysis of these trials by the Cochrane Collaboration concludes that there is no benefit from lowering the homocysteine level.[13]

References

  1. ↑ Anonymous (2024), Homocysteine (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. ↑ Anonymous (2024), Homocysteine (English). Medical Subject Headings. U.S. National Library of Medicine.
  3. ↑ 3.0 3.1 3.2 Wald DS, Wald NJ, Morris JK, Law M (November 2006). "Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence". BMJ 333 (7578): 1114–7. DOI:10.1136/bmj.39000.486701.68. PMID 17124224. PMC 1661741. Research Blogging.
  4. ↑ Anonymous (2024), Hyperhomocysteinemia (English). Medical Subject Headings. U.S. National Library of Medicine.
  5. ↑ Homocysteinemia. Online Mendelian Inheritance in Man. Retrieved on 2008-11-16.
  6. ↑ 6.0 6.1 Wald DS, Law M, Morris JK (November 2002). "Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis". BMJ 325 (7374): 1202. PMID 12446535. PMC 135491. [e]
  7. ↑ 5,10-@methylenetetrahydrofolate reductase; MTHFR. Online Mendelian Inheritance in Man. Retrieved on 2008-11-16.
  8. ↑ Jamison RL, Hartigan P, Kaufman JS, et al (September 2007). "Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial". JAMA 298 (10): 1163–70. DOI:10.1001/jama.298.10.1163. PMID 17848650. Research Blogging.
  9. ↑ 9.0 9.1 Ebbing M, Bleie Ø, Ueland PM, et al (August 2008). "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial". JAMA 300 (7): 795–804. DOI:10.1001/jama.300.7.795. PMID 18714059. Research Blogging.
  10. ↑ Bønaa KH, Njølstad I, Ueland PM, et al (April 2006). "Homocysteine lowering and cardiovascular events after acute myocardial infarction". N. Engl. J. Med. 354 (15): 1578–88. DOI:10.1056/NEJMoa055227. PMID 16531614. Research Blogging.
  11. ↑ McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM (June 2006). "A controlled trial of homocysteine lowering and cognitive performance". N. Engl. J. Med. 354 (26): 2764–72. DOI:10.1056/NEJMoa054025. PMID 16807413. Research Blogging.
  12. ↑ Aisen PS, Schneider LS, Sano M, et al (October 2008). "High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial". JAMA 300 (15): 1774–83. DOI:10.1001/jama.300.15.1774. PMID 18854539. Research Blogging.
  13. ↑ Martí-Carvajal AJ, Solà I, Lathyris D, Salanti G (2009). "Homocysteine lowering interventions for preventing cardiovascular events.". Cochrane Database Syst Rev (4): CD006612. DOI:10.1002/14651858.CD006612.pub2. PMID 19821378. Research Blogging.
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