Why worry about Low Homocysteine?

High plasma homocysteine is widely recognized as a cardiovascular disease risk factor, individuals with low homocysteine may also be at risk. The risk of hypohomocysteinemia derives from the fact that homocysteine is the normal intermediate for conversion of methionine into cysteine, and thus for production of glutathione, taurine and sulfate. Individuals with low homocysteine have limited capacity for response to oxidative stress and certain kinds of toxin exposure. 

Low homocysteine can restrict the amount of glutathione that can be produced in response to oxidative stress. Two additional detoxification factors,taurine and sulfate, are  produced from cysteine (and therefore, also influenced by low homocysteine)  Hypohomocysteinemia causes reduced availability of cysteine.  Cysteine restriction causes limitation in production of sulfate, taurine and glutathione.  The limited production ability is exacerbated in conditions that cause increased demand for any of the sulfur compounds produced from homocysteine.  One of the body’s main uses of sulfate and taurine is in Phase II liver detoxification. Taurine is involved in the formation of bile acids whereas the sulfation pathway is required for removal of steroid hormones, phenolic compounds and numerous drugs. Glutathione metabolic activities include Phase II conjugation reactions, prostaglandin synthesis and reduction/oxidation reactions. Indeed, a survey of the literature shows that a reduction in glutathione is associated with diseases impacting virtually every major organ system.

1. Huang J, Khan S, O’Brien PJ: The glutathione dependence of inorganic sulfate formation from L- or D-cysteine in isolated rat hepatocytes.Chem Biol Interact 1998, 110(3):189-202.

2. Kalantar-Zadeh K, Block G, Humphreys MH, McAllister CJ, Kopple JD: A Low, Rather than a High, Total Plasma Homocysteine is an Indicator of Poor Outcome in Hemodialysis Patients J Am Soc Nephrol 2004, 15:442-53.

3. Kalantar-Zadeh K: Recent advances in understanding the malnutritioninflammation-cachexia syndrome in chronic kidney disease patients:Semin Dial 2005, 18(5):365-9.

4. Lang CA, Mills BJ, Mastropaolo W, Liu MC: Blood glutathione decreases in chronic diseases.J Lab Clin Med 2000, 135(5):402-5.