What Supplements Should You Take if You Have a CBS Mutation?
The CBS gene is an incredibly important gene that can affects things like your mood, perceived energy levels, susceptibility to heart disease and cancer, your ability to tolerate high protein diets, and a lot more.
Some background:
The CBS gene produces the CBS enzyme (short for Cystathionine-β-synthase) that sits right at the crossroads of two essential biochemical processes:
Homocysteine removal
and
Glutathione generation.
In other words, it’s involved in removing something “bad”—homocysteine—and producing something “good”—glutathione.
Homocysteine is a highly studied chemical in the body that has the potential to harm the health of your brain, heart, blood vessels, and much more.
Glutathione is known as the “master antioxidant.” It removes toxins from the body, regulates neurotransmitters in the brain, and helps you fight off viruses.
If you have a “mutation” in the CBS gene (which is really just a problematic variant, not a “mutation”), that means that you have one of two issues:
Your CBS enzyme breaks down homocysteine and produces glutathione too slowly—meaning too much homocysteine and too little glutathione. I’ll call this SLOW CBS.
Your CBS enzyme breaks down homocysteine and converts it into glutathione too quickly. I’ll call this FAST CBS.
Number 1 is, generally speaking, the bigger problem, and it’s what I’m going to focus on in this article.
Firstly, how do you know you have a slow CBS variant?
I’m not going to focus too much on this in this article, but suffice it to say that I see two main ways to assess your CBS activity:
(1) Genetic Analysis. This means basically looking at which version of this gene you inherited from your parents. You can look at many different “spots” (SNPs) on the DNA to help assess your CBS variant, but the C699T SNP at rs234706 appears to be the most studied. If you have two “G” alleles at that spot (one from each parent), that suggests that you have a slower version of the CBS enzyme.
(2) Biomarker Analysis. What I do here is compare the levels of homocysteine and cystathionine in your bloodstream. A high ratio of homocysteine to cystathionine is suggestive of slower CBS function. Our Ultimate Methylation Package tests these biomarkers.
What do you do about a slow CBS? What supplements should you take to deal with this CBS gene “mutation,” as it is incorrectly referred to on the media by influencers like Gary Brecka?
Overall, I consider the most important supplements to take for CBS mutations to be vitamin B6, glycine, and zinc—but these have to be done the right way.
Of these, perhaps the most important—and the hardest to get right—is vitamin B6.
Optimizing Vitamin B6 is one of the most important factors involved in addressing a slow CBS variant.
The CBS enzyme is dependent on vitamin B6 to function properly. Higher levels of vitamin B6 mean higher activity of the CBS enzyme, lower homocysteine, higher glutathione, and improved symptoms in the realms of brain function, energy, mood, detoxification, and more.
B6 is itself a cofactor for CBS—i.e. CBS requires B6 to attach to it in order to function properly.
However, this B6 has to be in its active form, which is pyridoxal-5-phosphate, also known as P5P or PLP. More on this later.
Therefore, if you have a deficiency of B6, specifically pyridoxal-5-phosphate, your CBS enzyme will not function properly, and you will accumulate homocysteine and be unable to effectively produce glutathione.
Is the solution to this high-dose vitamin B6 supplementation?
For some people, yes, but not for all. High-dose B6 supplementation, when done wrong, can lead to the unpleasant paradox of vitamin B6 toxicity, a growing population-wide problem of its own.
The key is to supplement with just the right amount and form of vitamin B6, while also taking the required cofactors for effective B6 utilization.
How to supplement Vitamin B6 for optimal CBS function
To reiterate, vitamin B6 needs to be in its active, pyridoxal-5-phosphate (P5P) form to be able to improve CBS function. This is in contrast to the form of vitamin B6 most commonly available in supplements, which is the inactive pyridoxine HCl form.
Does this mean you should just take P5P?
Not necessarily. In fact, it’s theorized that the body may actually absorb pyridoxine HCl (the inactive B6) into the bloodstream more effectively than it does P5P. This—and other, more complex matters that I may write about later on—may make pyridoxine a better choice for some people.
But, all things considered, P5P is overall likely a better choice for most.
However, to avoid developing toxicity from it, it’s important to take the appropriate measures.
Get a blood test of at least your plasma vitamin B6 and vitamin B5 prior to supplementation. Ideally, you should test even more: A full B vitamin panel, mineral panel (both extra- and intra-cellular minerals, ideally), and CMP are a good place to start.
Start with low dosages of P5P. Around 5 mg per day is a good place to start, taken alongside 250-500 mg of Pantothenic Acid, on an empty stomach.
The effect of zinc on the CBS enzyme
Zinc is, in my opinion, a highly important but often-overlooked means for addressing CBS variants.
Unlike vitamin B6 (P5P), zinc is not a cofactor for the CBS enzyme—and I think that explains why it’s often overlooked. You won’t find anything on zinc, in fact, on most of the most popular articles on the CBS gene on the internet.
But zinc is vitally important, not in its own right, but because of its effects on vitamin B6.
Zinc is required for your body to be able to turn inactive vitamin B6 into active pyridoxal-5-phosophate. Without enough zinc—even if you’re consuming a vitamin B6-rich diet—you won’t get enough zinc to actually effectively activate B6 to then activate the CBS gene, and you’ll be left with high levels of homocysteine and low levels of the “master antioxidant,” glutathione.
In fact, I theorize that some of the associations found in the research between low zinc and high homocysteine levels is due to its effect (albeit, indirect) on the CBS enzyme.
I generally recommend supplementing with zinc at a dosage of around 10-25 mg per day (with food). You don’t want to take too much as that can actually cause other nutrient deficiencies.
Avoid zinc picolinate—one of the most common forms of zinc on the market—as it appears to be poorly utilized by the body, contrary to what many believe.
Zinc bisglycinate tends to be a good option, in my opinion.
Glycine is also an important supplement for slow CBS mutations.
Glycine is another underestimated component of the slow-CBS plan.
But its utility here should be obvious, for the physiology is simple: In the process of converting homocysteine into cystathionine (and thus clearing homocysteine from the system and preparing it for the production of glutathione), the CBS enzyme uses the amino acid serine.
In other words, serine must be there for CBS do its job.
I’ve had a lot of patients with low serine levels—it’s actually more common than you may think—and that suboptimal serine status can absolutely contribute to CBS dysfunction.
Where does glycine come into play here? Glycine and serine are interconverted within the body. If the body doesn’t have enough glycine, it makes more using serine, and vice versa.
So, while supplementing with serine would arguably more directly help modulate CBS function, glycine may be nearly as good in this regard, and you also get a lot of other benefits from glycine supplementation.
And low glycine (and thus serine) levels are only to be expected nowadays, especially given the fact that people barely consume organ meats, skin, bones, and other animal connective tissues as much as they used to, all of which are the main sources of glycine in the diet.
NEW: If you’d like to learn to address your methylation and COMT function without genetic testing, check out my 5-Week Methylation + COMT Master Plan.
A note from Dr. Malek:
If you’re interested in helping support my work, the best thing you can do is help share my website. Consider linking my blog posts on your social media pages, reddit forums, etc. (and feel free to @ me on your posts). It’s not easy competing with multimillion-dollar healthcare behemoths, so your help in amplifying a relatively small voice really goes a long way. Thank you :)
~Dr. Malek
Keep in mind that this is not official medical advice. No doctor-patient relationship is established through this article or through any other information provided on this website.
