Sometimes when you are getting started with learning about a new topic, such as genetics and 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 kind of interesting, even if it isn’t exactly in line with the headlines on other websites that scream ‘Fix this first!’.

CBS Gene: Function and Research Studies

What is the CBS gene?

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.

What do online clinicians say about the CBS gene?

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:

  • Dr. Jocker’s recommending low sulfur diet: “The CBS mutation leads to excess taurine, ammonia and sulfur groups that are released into toxic sulfites in the body.  If the individual is consuming large amounts of sulfur containing foods it can lead to more sulfites and increased stress and inflammation”
  • MTHFR Support’s recommendation to ‘fix’ CBS first: “There is still much more for me to learn but one thing I do know, is that CBS must be addressed before an MTHFR, MTRR and/or and MTR protocol can be properly started….I am in contact with many doctors who know about CBS and SUOX who get an overflow of patients with negative side effects to an MTHFR protocol because their doctor did not address CBS and SUOX mutations first.”
  • Heartfixer site: “The CBS C677T and A360A genes code for enzyme function that is pathologically up regulated.  They are “always on” above that called for by the presence of oxidative stress.  Of the two, the C677T allele is the most important, producing enzyme activity that is 10 fold greater than normal”


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.

CBS Genetic Variants

Check your 23andMe data for rs234706 C699T (v4, v5):

  • A/A: associated with increased LDL and triglyceride levels [ref], decreased risk of cleft lip
  • A/G: associated with increased LDL and triglyceride levels
  • G/G: normal

Studies on this variant show:

  • A large genome-wide association study found the minor allele (A) to be associated with increased total cholesterol, increased LDL-c and increased triglyceride levels. [ref]
  • Mothers who carry the minor allele were less likely to have a baby with a cleft lip with those carrying two copies (A/A genotype) having half the normal risk. [ref]
  • Pregnant women who carry the risk allele were at an increased risk of mild, late-onset preeclampsia.[ref]

Check your 23andme data for rs1801181 A360A(v4 only):

  • A/A: slight statistical increase in risk of lymphoma[ref]
  • A/G: normal
  • G/G: normal

Check your 23andMe data for rs4920037 (v4, v5):

  • A/A: better arsenic detoxification [ref]
  • A/G: better at arsenic detoxification
  • G/G: normal

Check your 23andMe data for rs234709 (v4, v5):

  • T/T: better arsenic detoxification [ref]
  • C/T: better at arsenic detoxification
  • C/C: normal

Check your 23andMe data for rs5742905 I278T (v4 only):

  • G/G: increased homocysteine, responsive to vitamin B6[ref][ref]
  • A/G: increased homocysteine, responsive to vitamin B6
  • A/A: normal



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.  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.

1 Comment

Jenelle Sapier · April 2, 2019 at 6:12 pm

I am a 43 year old female and I have an 8 year old autistic daughter. We need testing and treatment for genetic mutations. I reside in Southern California and am unaware of how to get assistance and was wondering if you are able to assist me. Could you please contact me via email ? Thanks.

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