Homocysteine
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Homocysteine is an amino acid produced in the body during the metabolism of methionine, an essential amino acid obtained from dietary protein.(1) It is increasingly recognized as a predictor of potential health problems,such as cardiovascular diseases and cognitive disorders like Alzheimer’s disease.(2),(3). Elevated levels of homocysteine, known as hyperhomocysteinemia, are associated with various health issues, including strokes, memory decline, and complications in pregnancy(3),(4).
Key Points About Homocysteine
Metabolism and Regulation:
Homocysteine levels are influenced by several vitamins, particularly B6, B12, and folate. Deficiencies in these vitamins can lead to elevated homocysteine levels, as the body relies on them for its conversion processes.(1)
Health Risks
Higher levels of homocysteine are linked to vascular damage, which can increase the risk of coronary heart disease, strokes, and potentially contribute to neurodegenerative diseases. Even small increases in homocysteine levels can significantly elevate disease risk. One mechanism by which homocysteine is thought to cause this damage is by interfering with the way cells use oxygen, resulting in a build-up of damaging free radicals. Oxidation triggers many diseases including heart disease, strokes, cancers and autoimmune diseases.(2)
Factors Influencing Levels
Lifestyle choices such as poor diet, smoking, excessive alcohol consumption, and certain medications like corticosteroids can increase homocysteine levels. Family history and genetic factors also play a role, particularly variations in genes related to homocysteine metabolism.Additional factors include diabetes, rheumatoid arthritis, poor thyroid function,chronic inflammatory conditions and some intestinal disorders such as coeliac and Crohn’s diseases.Levels increase with age and higher levels are more common in men than women.(1)
Testing
Measuring homocysteine levels in the blood can be challenging due to sample handling requirements. A fasting sample is typically recommended to ensure accurate readings. After blood sampling the blood cells produce and release homocysteine resulting in an increase in measured levels which equates to about 10% per hour at room temperature. Thus it is important to separate the plasma(EDTA or heparinised) within 30 minutes of collection.Collection of blood serum is not appropriate due to the relatively long clotting time required. Once separated from the blood cells the homocysteine is stable in plasma for at least 4 days at room temperature, and much longer refrigerated or frozen.(1)
The increased need in clinical chemistry laboratories for methods of homocysteine determination, has led to the development of different analytical methods for measurement.
Methods include amino acid analysis, high performance liquid chromatography (HPLC), capillary electrophoresis, gas chromatography-mass spectrometry (GC-MS) and immunoassay. HPLC is the gold standard reference method. Different total homocysteine measurement methods do usually give comparable results.(1)
Normal Reference Ranges
There is no consensus about the upper reference limits for plasma homocysteine concentrations. Among apparently healthy individuals “normal” concentrations commonly range from 5 to 15µmol/L. It is clear now that each increase of 5µmol/L in homocysteine level increases the risk of coronary heart disease events by approximately 20%, independently of traditional coronary heart disease risk factors.(1)
Management
High homocysteine levels can often be managed through dietary changes and supplementation with B vitamins and other nutrients. Regular testing can help tailor these interventions to individual needs.
Research and Guidelines
Ongoing research is needed to clarify the mechanisms by which homocysteine affects health and to establish standardized guidelines for screening and management.
Overall, understanding and monitoring homocysteine levels can be an important part of assessing and managing health risks, especially for those with additional risk factors for cardiovascular and cognitive diseases.
References
(1) Rasmussen, K. and Møller, J. “Total homocysteine measurement in clinical practice”. Annals of Clinical Biochemistry, 2000, 37: 627-648.
(2) de Ruijter, W. et al, “Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study”. British Medical Journal, 2009, 338: a3083..
(3) Seshadri, S. et al, “Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease”. New England Journal of Medicine, 2002, 346:476-483.
(4) Rugolo, S. et al, “Hyperhomocysteinemia: associated with obstetric diabetes and fetal malformations”. Minerva Ginecologica, 2005, 57:619-25..
(5) Bolander-Gouaille, C. In “Focus on homocysteine and the vitamins involved in its metabolism”. Published by Springer-Verlag, France, 2002, Chapter 3, p33.
