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, when first learning about genetics and the methylation cycle.
The CBS gene often is referred to in relation to the methylation cycle. Certain websites and social media sites promote specific diets (low meat, low sulfur). Some try to sell specific supplements marketed to people who carry CBS genetic variants.
This article delves into the peer-reviewed research studies on the CBS genetic variants and discusses what the evidence shows.
CBS Gene: Does Research Show that You Should Eat a Low Sulfur Diet?
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”
NOTE that many of the methylation cycle websites haven’t been updated recently.
But what does research actually show on the CBS 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
Check your genetic data for rs234706 C699T (23andMe v4, v5; AncestryDNA):
- 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: typical
Members: Your genotype for rs234706 is —.
Note that about a third of the population carries the C699T variant.
Studies on the rs234706 variant show:
- A large genome-wide association study found an association with the minor allele (A) and 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.[ref]
- Pregnant women who carry the risk allele were at an increased relative risk of mild, late-onset preeclampsia.[ref]
Check your genetic data for rs1801181 A360A (23andme v4; AncestryDNA):
- A/A: a slight statistical increase in the risk of lymphoma with low B6 levels[ref]
- A/G: typical
- G/G: typical
Members: Your genotype for rs1801181 is —.
Other CBS SNPs:
Check your genetic data for rs4920037 (23andMe v4, v5; AncestryDNA):
- A/A: better arsenic detoxification[ref]
- A/G: better at arsenic detoxification
- G/G: typical
Members: Your genotype for rs4920037 is —.
Check your genetic data for rs234709 (23andMe v4, v5; AncestryDNA):
- T/T: better arsenic detoxification[ref]
- C/T: better at arsenic detoxification
- C/C: typical
Members: Your genotype for rs234709 is —.
Check your genetic data for rs5742905 (23andMe v4 only):
- G/G: risk of increased homocysteine, responsive to vitamin B6[ref][ref]
- A/G: risk of increased homocysteine, responsive to vitamin B6
- A/A: typical
Members: Your genotype for rs5742905 is —.
If you carry the rare rs5742905 variant that increases the risk of high homocysteine, you may want to get your homocysteine levels checked. If you are in the US, you can order a lab test yourself through UltaLabs or other online lab test retailers. Or, get your doctor to order one for you the next time you go for a check up.
A well-researched connection between high homocysteine and an increased risk of heart disease exists. If you do have the variant and high homocysteine levels, the good news is that vitamin B6 is likely to help.
Diet for CBS C699T or A360A:
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. A low sulfur-diet may help some people for other reasons, but the evidence doesn’t support the CBS genetic variants as a problem.
Instead, if you have other methylation cycle variants, you may want to focus on eating a choline-rich diet or a folate-rich diet.
Related Genes and Topics:
MTHFR: How to Check Your Data
It is easy to check your genetic results on 23andMe or AncestryDNA for the two main MTHFR variants known as C677T and A1298C. If you have 23andMe results (it doesn’t matter if you have the health option or not!), click on the link below to check your MTHFR gene.
COMT and supplement interactions
People with a slow COMT enzyme function may have problems when taking high doses of methylation cycle supplements or certain anti-inflammatory supplements.
Heart disease is the leading cause of death in the US and around the world, and high LDL-cholesterol levels have been linked in many studies to increased heart disease. Learn how your genes impact LDL levels.