A thiol containing amino acid intermediate which is formed during the metabolism of the essential amino acid methionine.
An intermediary amino acid formed during the metabolism of methionine, an essential amino acid derived from protein.
High levels associated with meat eating.
Elevated homocysteine levels have also been identified as an independent risk factor for cardiovascular disease.
A high level of homocysteine is a risk factor for heart disease, and is associated with low levels of vitamins B6, B12, and folate, as well as renal disease.
Homocysteine is a sulfur-containing amino acid derived from methionine that is normally present in blood.
Elevated homocysteine levels are thought to promote thrombogenesis, impair endothelial vasomotor function, promote lipid peroxidation, and induce vascular smooth muscle proliferation.
Lowering of homocysteine levels down does not reduce the chance of having heart disease.
There is a relationship between high levels of homocysteine and artery damage, lead ing to atherosclerosis.
Evidence from retrospective, cross-sectional, and prospective studies links elevated homocysteine levels with coronary heart disease and stroke
Experimental studies indicate homocysteine caused oxidative stress, endothelial injury and enhances thrombogenicity.
Children with inborn errors of homocysteine metabolism have high risk for atherosclerosis.
Plasma level elevations associated with increased coronary artery disease.
Elevated plasma levels associated with poor recall.
Inversely associated between plasma levels and assessed cognitive function.
Some studies have shown elevated levels in people with Alzheimer’s disease.
There is a strong relationship between plasma levels and the risk of dementia and Alzheimer‘s disease (Seshadri).
Incremental increases in plasma levels of 5 micromol per liter resulted in an increased risk of Alzheimer’s disease by 40% (Seshadri)
Plasma levels in the highest quartile doubles the risk of dementia or Alzheimer’s disease.
Elderly individuals with elevated homocysteine levels (> 13 µmol/L) are almost twice as likely to show decline in memory and global cognition.
The body requires folate, vitamins B12 and B6, and S-adenosyl-L-methionine (SAMe) for normal production of serotonin, norepinephrine, and dopamine, and if this methylation cycle is not working adequately, the homocysteine level will rise.
Elevated homocysteine levels occur with poor nutrition, deficient cofactors (folate, B6, B12, SAMe), or genetic predisposition (MTHFR [methylenetetrahydrofolate reductase] gene defect).
Vitamin B12, folate, and vitamin B6 are involved in homocysteine metabolism.
Eating foods rich in folate, such as dark, leafy greens, and eating foods rich in B-vitamins, including nuts, beans, whole grains, lean meat, and fish can keep homocysteine levels low.
With elevated homocysteine avoiding prolonged acid suppression is warranted , as acid is needed for B-vitamin absorption.
Supplemental with vitamin B12 500–1000 µg, B6 50 mg, and folic acid 1 mg. can reduce homocysteine levels, but require higher doses of folic acid to lower homocysteine.
Combinations of vitamin B12 and folic acid supplements with or without vitamin B6 decrease homocysteine levels in people with vascular disease or diabetes and in young adult women.
Older men and women who take a multivitamin/multimineral supplement for 8 weeks experience a significant decrease in homocysteine levels.
The active form of folate is methylfolate (MTHF) and it is the methylfolate that crosses the blood–brain barrier.
In patients with poor cognition and or depression MTHF, 5–15 mg daily should be considered.
Depression and high total plasma homocysteine are independently associated with cognitive impairment in older adults.
Plasma levels-strong correlation between total homocysteine level cardiovascular and all-cause mortality.
Direct association between blood levels and risk of age related macular degeneration.
High levels of plasma homocysteine associated with risk of developing diabetic neuropathy, retinopathy, myocardial infarction and stroke.
A meta-analysis of prospective studies indicated a 25% lower homocysteine concentration was associated with 11% lower risk of coronary artery disease and a 19% lower risk of stroke (Homocysteine Studies Collaboration).
Long term reduction in homocysteine blood levels with B12 and folic acid supplementation does not have beneficial effects on vascular outcomes (Search of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group): Double blind controlled study of 12,064 survivors of myocardial infarction in the UK, with 6.7 years of follow-up.
Evidence supports folic acid and vitamin B12 supplements can lower homocysteine levels, but studies have not shown that these supplements decrease the risk of cardiovascular disease.
The Heart Outcomes Prevention Evaluation (HOPE) 2 trial, which included 5,522 patients older than 54 years with vascular disease or diabetes, found that daily treatment with 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 for an average of 5 years reduced homocysteine levels and the risk of stroke but did not reduce the risk of major cardiovascular events.
In a multicenter, randomized double blind, placebo controlled trial with vitamin B-folic acid, vitamin B6, and vitamin B12 in diabetic with Type I and Type II diabetes with diabetic nephropathy: high doses of vitamin B resulted in a greater decrease in GFR and increase in vascular events (Diabetic Intervention with Vitamins to Improve Nephropathy), despite significantly lowering plasma total homocysteine.
Plasma levels a strong predictor of mortality in coronary artery disease and aortic valve stenosis.
Levels increase with age, inactivity, smoking, excessive coffee consumption and chronic heavy alcohol consumption.
Total levels associated with increased risk of atherosclerosis sequelae including death from cardiovascular processes, coronary heart disease, carotid vascular disease and stroke.
In non-diabetic at-risk patients with homocysteine levels higher than 15 micromol/L have been shown benefit from treatment with folic acid.
Concentrations can be lowered with either folic acid or vitamin B12 supplementation or a combination of both.
Plasma concentrations of homocysteine are lowered by vitamin B therapy and improves endothelial function.
0.5-5.0 mg of folic acid supplementation typically lowers plasma homocysteine levels by 25%.
Vitamin B12 supplementation of at least 0.4 mg daily to folic acid reduces plasma levels by an additional 7 percent.
Vitamin B6 supplements may lower homocysteine levels after methionine loading.
Associated with a higher risk of ischemic myocardial injury in patients presenting with acute coronary artery syndromes.
Levels elevated with hypothyroidism, menopause and with low levels of B6, B12, and folate.
Elevated levels in ESRD.
Folic acid, pyridoxine and vitamin B12 reduce levels and may reverse endothelial injury associated with elevated homocysteine levels.
Secondary trials of folic acid with or in combination with vitamin B12 and or vitamin B6 have not improved risk of cardiovascular disease, stroke or mortality.
Daily supplementation with folic acid can lower homocysteine levels by about 25%, and the addition of vitamin B 12 lowers it by another 7%.
Elevated levels associated with a 4.5 times risk of Alzheimer’s disease.
Its role in atherogenesis has not yet been established.
Potential mechanisms of vascular disease include damage and dysfunction to the endothelium, vascular smooth muscle proliferation, increased platelet aggregation, activation of factor V and protein C inhibition.
Despite reduction in homocysteine levels with daily administration of folic acid, vitamin B12 and vitamin B6 the incidence of stroke, myocardial infarction and cardiovascular deaths were not reduced after 5-years of follow-up in the Heart Outcomes Prevention Evaluation 2 study.
In a randomized, double blind controlled trial in Norway-Western Norway B Vitamin Intervention Trial (WENBIT), with 3096 adult patients undergoing coronary angiography randomized to assess the effect of treatment with vitamin B6, folic acid, vitamin B12, or placebo: no effect of treatment with B6, B12 or folic acid was noted on mortality or cardiovascular events during a median follow-up of 38 months (Ebbing).
Plasma levels associated with the quantity of coronary artery calcification in patients at intermediate risk of coronary heart disease at 10 years, but not for those at low or high risk.