Wow, this morning I got this blast from the past: my colleague surfaced and sent me a 2006 paper I had co-authored with the esteemed Dr. Richard Lord, who was my post-grad supervisor at the time and is my mentor still, on the risks of having your homocysteine run too low.
The issue of having too little homocysteine is still as relevant now, as it was then. In the excitement over reducing a high homocysteine, and overcoming methylation deficits, it’s easy to forget that homocysteine still has a positive role to play.
I wanted to share with you some excerpts from this paper, which you can also find in full here.
In opposition to transmethylation, homocysteine undergoes transsulfuration forming cystathionine (Figure 1). Through this pathway, homocysteine is an intermediate in the conversion of methionine to cysteine. A sensitive enzyme regulation mechanism controls whether homocysteine is predominantly transmethylated or transsulfurated. The function of this regulation is to allow rapid response to oxidative challenge by increasing the formation of glutathione, a process dependent on cysteine availability (Figure 2). Restriction of the substrate (homocysteine) can limit the formation of the product (glutathione). This means that a 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) .
While 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. The most common treatment for low homocysteine is administration of sulfur-containing amino acids such as methionine, N-acetylcysteine and taurine. Preformed glutathione and inorganic sulfate salts (potassium sulfate) may also be employed. Plasma methionine and urinary sulfate, pyroglutamate or alpha-hydroxybutyrate are related tests that may be performed for confirmation of significant cysteine deficit.
How low is too low? Data suggests that a low limit of 4.0 nmol/mL should be what flags you to a homocysteine level that indicates a potential need for support, either supplemental and/or diet/lifestyle.
And if you’re wondering what my upper range for homocysteine is, I like to see it below 7.0 nmol/mL.
Find out more about advanced metabolic and epigenetic methylation support here.