Homocysteine
The amino acid whose elevated levels accelerate vascular and brain ageing
Definition
Homocysteine is a sulfur-containing amino acid intermediate of methionine metabolism. Its plasma accumulation (hyperhomocysteinemia) is toxic to vascular endothelium: it causes oxidative stress, endothelial dysfunction, inhibition of nitric oxide synthesis, and promotion of thrombogenesis. Levels >10 μmol/L are associated with increased risk of cardiovascular disease, stroke, dementia, osteoporotic fractures, and accelerated brain atrophy. It is one of the few biomarkers with simple, highly effective dietary intervention.
Detailed explanation
Metabolic pathways: homocysteine is metabolised through two routes — remethylation (returned to methionine, requires folate, B12, and betaine) and trans-sulfuration (converted to cysteine, requires B6). Deficits of these vitamins (especially folate and B12) are the most common cause of hyperhomocysteinemia.
MTHFR gene mutations (rs1801133, C677T) reduce methylenetetrahydrofolate reductase activity by up to 70% in TT homozygotes (approximately 10% of Europeans), interfering with folate metabolism and chronically elevating homocysteine. These patients require active forms: methylfolate (5-MTHF) and methylcobalamin, instead of synthetic folic acid and cyanocobalamin.
Longevity targets: homocysteine <8 μmol/L (not just <15 μmol/L of the lab range). Studies such as OXFORD VITACOG (2010) showed that lowering homocysteine with B vitamins significantly reduces brain atrophy in mild cognitive impairment.
Nutritional protocol: methylfolate 800 μg/day, methylcobalamin 500-1000 μg/day, pyridoxal-5-phosphate 25-50 mg/day (active form of B6), riboflavin 100 mg/day (MTHFR cofactor), trimethylglycine/betaine 1-3 g/day. Re-check at 12 weeks. If still elevated, evaluate renal function, hypothyroidism, and excess coffee consumption (>5 cups/day raises homocysteine).
Scientific sources
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