CBS Genetic Variants: Should you eat a low sulfur diet?

When you start to learn 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 too, when first learning about genetics and the methylation cycle. The CBS gene often is talked about in relation to the methylation cycle. Certain websites and online forums promote specific diets (low meat, low sulfur) or sell specific supplements marketed to people who carry genetic variants. This article delves into the peer-reviewed research studies on the CBS genetic variants and discusses what the evidence shows.

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 transsulfuration 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 participates in a desulfation reaction to help create hydrogen sulfide, H2S.  Hydrogen sulfide, a molecule needed by the body in just the right amount, at low levels, acts as a mitochondrial electron donor, but at high levels, it is poisonous to the mitochondria. Likewise, the importance of the body maintaining the right levels of homocysteine should not be understated because high levels of homocysteine are associated with heart disease.[ref] Changes in CBS enzyme production show connections to a variety of problems including cardiovascular disease and immune system problems.  Decreased CBS causes homocysteine levels to rise, leading to homocystinuria. Something to note here, 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"

Research Studies on CBS Gene Variants

Surprisingly, there isn't a ton of research on the CBS variants on which the clinicians above are basing their recommendations for a low sulfur diet. There are studies on the variants - but they don't show that they have much of an impact on health. I encourage you to read the research for yourself and see what you think. I mentioned the articles above because the research on the variants:
  • does not show these variants are a problem
  • does not indicate that everyone with the variants should be on low sulfur or low protein diets
  • does not show that people with the variants should shell out money for specific ammonia reducing supplements
Instead, the research indicates that the common CBS variants may have a subtle effect on cholesterol levels. One of the variants slightly decreases the risk of having a baby with a cleft lip.[ref][ref]  

CBS Genetic Variants

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