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It’s only fairly recently that homocysteine has joined the likes of cholesterol and high blood pressure as a significant risk factor for heart disease. Yet the homocysteine theory was first proposed way back in 1969 by the pioneering Dr Kilmer McCully MD. He had been studying a rare genetic disorder known as homocysteinuria where children are born lacking the enzymes to covert potentially harmful homocysteine into harmless substances. Unless diagnosed and treated, these children often suffer from early fatal heart attacks and strokes. Whilst this condition is fortunately very rare, Dr McCully started to investigate whether levels of homocysteine could potentially build up in otherwise healthy people and increase their heart disease risk. Many years later, large scale research studies have confirmed his theory and homocysteine is now considered a significant risk factor for heart disease, perhaps even as much as smoking.

Homocysteine is an amino acid derived from methionine, an amino acid found in animal proteins. During normal metabolism, any excess homocysteine is safely eliminated with the help of B6, B12 and folic acid in particular. However, if this process is disrupted, either by nutrient deficiencies, sub-functioning enzymes or unhealthy lifestyle factors, levels of homocysteine can build up and significantly increase heart disease risk. We now know that homocysteine is a very toxic molecule which can cause the initial damage to the artery wall that starts the whole process of cardiovascular disease.  

Key nutrients are needed for optimal homocysteine metabolism, and in fact, nutritional intervention is the only therapy that has proven effective in reducing levels. There are two main pathways for the safe conversion of homocysteine. It can be methylated to form methionine via methionine synthase, or it can be converted to cystathionine (which in turn can be converted to cysteine) by the enzyme cystathionine βsynthase (CBS).

Key nutrients for homocysteine metabolism:

  • Vitamin B6 (Pyridoxal 5 Phosphate) – Essential for the safe conversion of homocysteine into cystathionine and then cysteine.
  • Folic Acid – Perhaps the most significant nutrient to support healthy homocysteine levels. It is essential to support the remethylation of homocysteine to methionine. A 14-year prospective cohort study published in JAMA found that higher intakes of folate, alone or in combination with vitamin B6 substantially lowered rates of coronary heart disease1.  
  • Vitamin B12 – Works with folic acid for the conversion of homocysteine into methionine.
  • Betaine – Acts as a methyl donor in the metabolism of homocysteine to methionine. Research shows that long-term betaine supplementation substantially lowers plasma homocysteine levels2.

1.    Rimm E. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998;279:359- 364.
2.    Wilken DE, Dudman NP, Tyrrell PA. Homocystinuria due to cystathionine beta-synthase deficiency – the effects of betaine treatment in pyridoxine-responsive patients. Metabolism. 1985;34:1115-1121.

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