When you are getting started with learning about the methylation cycle, it is easy to jump on board with whatever is being parroted by the experts who have pretty websites (and supplements to sell you). This was true for me when starting off learning about genetics and the methylation cycle.
The CBS gene is one that is often talked about in relation to the methylation cycle. I have been avoiding writing about this gene because I hadn’t been able to find a lot of research studies to back up the ideas being promulgated by all the online health gurus.
This article has been in my drafts folder for a year, but I’m finishing it up and publishing it today because the actual research on the CBS gene is interesting, even if it isn’t doesn’t back up the headlines on other websites that scream ‘Fix this first!’.
The CBS gene – cystathionine beta-synthase – codes for the CBS enzyme that acts within the transulfation pathway. The CBS enzyme reduces homocysteine to an intermediate (cysteine) that eventually can become glutathione, an important antioxidant in the body. Additionally, the CBS enzyme is involved in a desulfation reaction that creates hydrogen sulfide, H2S. Hydrogen sulfide is a molecule that is needed by the body in just the right amount: at low levels, it acts as a mitochondrial electron donor, but at high levels, it is poisonous to the mitochondria. Likewise, it is important for the body to maintain the right level of homocysteine, with high levels of homocysteine being associated with heart disease.[ref]
Changes in CBS enzyme production have been linked to a variety of problems including cardiovascular disease and immune system problems. Decreased CBS causes homocysteine levels to rise, leading to homocysteinuria.
Something to note here is that vitamin B6 is a cofactor, needed in the reaction that converts homocysteine.
CBS is often mentioned on websites that discuss the methylation cycle, with speculation by a couple of well-known clinicians that some of the variants listed below up-regulate or increase the amount of the CBS enzyme.
Websites that discuss these clinician’s ideas often caution against eating foods that contain sulfur (meat, garlic, eggs, etc) with the variants and warn of too much ammonia. Here are a few examples of what doctors are recommending:
I’m mentioning the other online articles because the research studies on the variants don’t back up the idea that the common CBS variants are a problem that needs to be fixed with a restrictive diet or ammonia reducing supplement. Could I be wrong? Of course. I encourage you to read the research for yourself and see what you think.
Check your 23andMe data for rs234706 C699T (v4, v5):
Studies on this variant show:
Check your 23andme data for rs1801181 A360A(v4 only):
Check your 23andMe data for rs4920037 (v4, v5):
Check your 23andMe data for rs234709 (v4, v5):
Check your 23andMe data for rs5742905 I278T (v4 only):
If you carry the rs5742905 variant that increases the risk of high homocysteine, it would be a good idea to get your homocysteine levels checked. If you are in the US, you can order a lab test yourself through UltaLabs. Or get your doctor to order one for you.
High homocysteine is linked to an increased risk of heart disease. If you do have the variant and high homocysteine levels, the good news is that vitamin B6 is likely to help.
Otherwise, if you carry the C699T or A360A variants, there is no evidence that I can find that suggests that you should go on a restrictive, low-sulfur diet.