From the Guidelines
Elevated homocysteine levels can result from several factors, including genetic mutations, nutritional deficiencies, certain medications, medical conditions, and lifestyle factors. The most significant causes of elevated homocysteine levels include genetic mutations in the MTHFR gene, nutritional deficiencies of vitamin B12, folate, and vitamin B6, and certain medical conditions such as hypothyroidism, kidney disease, and psoriasis 1. Some key factors that contribute to elevated homocysteine levels are:
- Genetic mutations in the MTHFR gene
- Nutritional deficiencies of vitamin B12, folate, and vitamin B6
- Certain medications such as methotrexate, phenytoin, and proton pump inhibitors
- Medical conditions like hypothyroidism, kidney disease, and psoriasis
- Lifestyle factors including smoking, excessive alcohol consumption, and high coffee intake
- Age, as homocysteine levels naturally increase with age Treatment typically involves addressing the underlying cause, often through B vitamin supplementation, dietary improvements, and lifestyle modifications 1. Regular monitoring is crucial, especially for those with genetic predispositions or chronic conditions affecting homocysteine metabolism, to prevent the increased risk of atherosclerotic vascular disease, including stroke, associated with elevated homocysteine levels. It is essential to note that while B vitamin supplementation can lower homocysteine levels, its effect on reducing the risk of stroke is still inconsistent and requires further research 1. In clinical practice, the focus should be on identifying and addressing the underlying causes of elevated homocysteine levels, rather than solely relying on supplementation, to improve patient outcomes and reduce the risk of cardiovascular disease.
From the Research
Causes of Elevated Homocysteine
- Genetic mutations and enzyme deficiencies in 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS), and cystathionine β-synthase (CβS) 2
- Deficiencies in folate, vitamin B12, and to a lesser extent, deficiency in B6 vitamin 3, 2
- Inadequate nutrient status and lifestyle factors 3
- Systemic disease and various drugs 3
- Excessive methionine intake 4
- Renal impairment 2
- Rare but treatable inborn errors of metabolism (IEM) such as classic homocystinuria due to cystathionine beta-synthase deficiency 5
Pathological Significance of Hyperhomocysteinemia
- Trigger for many diseases, such as atherosclerosis, congestive heart failure, age-related macular degeneration, Alzheimer's disease, and hearing loss 4
- Connected with occlusive artery disease, especially in the brain, the heart, and the kidney, in addition to venous thrombosis, chronic renal failure, megaloblastic anemia, osteoporosis, depression, and pregnancy problems 2
- Reduced methylation potential (MP) induced by elevated plasma homocysteine levels seems to be the true responsible for cardiovascular diseases (CVD) 6
- DNA hypomethylation inducing an inhibition of cyclin A transcription and a reduction of endothelial cells growth 6