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

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!’.

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”

Research Studies on CBS Gene Variants

I mentioned the articles above 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.  Instead, the research indicates that the common CBS variants may have a subtle effect on cholesterol levels.

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.

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: a slight statistical increase in the 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

Lifehacks

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.  A low sulfur-diet may help some people for other reasons, but I don’t think these CBS genetic variants are the main culprit.



Wishing that you had an easy way to know which Genetic Lifehacks articles apply to you? Get a Genetic Lifehacks Ultimate Cheat Sheet that matches your data to all of the articles available.
 

Genetic Lifehacks Weekly Update

* indicates required

14 Comments on “CBS Genetic Variants: Should you eat a low sulfur diet?

  1. 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.

  2. I just wanted to share my story, I have mthfr c677t mutation, cbs mutation, mcas, pots, euthyroid sick syndrome and chronic dehydration with idiopathic origins. I had just tried the keto diet and 4 days in I became incredibly sick and went into a severe mast flare, I rechecked my genetic report to see if I had missed anything. That’s when I found the cbs mutation and switched to low sulfur diet and noticed immediate improvement in the previous symptoms. Maybe cbs mutation alone isn’t of concern but many people with mcas and cbs mutation do get very sick for high sulfur foods.

      • I am Homozygous for CBS699 and have at least 3 or 4 SUOX mutations in addition to a heterozygous MTHFR 1298 mutation.

        I have to absolutely avoid all foods high in sulfur and phosphorus as those acids cannot be excreted and build up in my cells and cause soft tissue calcification which leads to bad fibro pain.

        I cannot eat any vegetables at all because of this. I can only eat about 15 foods that won’t make me ill or cause pain. I only eat two starches (San Luis sourdough bread/ sourdough bread does not have phosphate chemical risers like all other breads) and I can eat potatoes because they are low in sulfur and phosphorus and that is it for starches

        As for salad stuff, celery, lettuce avocado and cilantro and thats it.

        As for veggies: none (all too high in sulfur and phosphorus for me)

        As for fruits: (oranges, apples, pears, mangoes, orange juice Odwalla)

        As for meats (I can eat meat in small quantities without developing ammonia breath. I eat beef and pork. I have to avoid chicken because all chicken now has trace amounts of MSG chemicals in it and I am severely allergic to MSG. And I avoid fish because it is high in sulfur and phosphorus)

        I avoid all nuts, all legumes, all dairy, all oatmeal and corn and rice, and all veggies.)

        Until I learned that I had a homozygous CBS699 mutation along with multiple SUOX mutations, I was always ill with utis and yeast infections and bad allergies and bad fibromyalgia pain and brain fog.
        And it was all caused by the excessive buildup of sulfur and phosphorus in my system due to these mutations.

        Now, I never get yeast infections or UTIs and my migraines and fibromyalgia pain and brain fog is all gone.

        My sulfite levels are still pretty high though even on my strict diet. I bought Quantofix sulfite strips to measure urinary sulfite and urinary sulfite is not supposed to go over a maximum of 400mg/ L (milligrams per Liter) and my urinary sulfite levels, even on my strict low sulfur low phosphorus diet are around 1600mg/L.

        So my body really has very little ability to rid itself of excess sulfite and phosphates.

        Getting my genes mapped and finding out about these mutations, as well as finding Dr. Jockers Webpage on diet for those with CBS 699 upregulations like I have has really helped.

        I also found a good book on how to prevent excess phosphates in the body and that has helped to, in fact it saved my life before I even had my genes mapped and knew for sure that it was mutations causing my problems.

        The book on excess phosphates is called: Calcification: The Phosphate Factor in Aging and Disease by Mark Mayer and you can get it on Amazon and I highly recommend it. The man is not credentialed but I am indebted to him and his info because it literally has save my life. (I do not however follow his advice on taking vitamin K and vitamin D because I have found that both of those supplements cause me bad pain, so I just avoid both and I also avoid all calcium and sulfur and phosphorus supplements as well)

        • Hi Rebecca,
          Thanks for posting all of this information about your reactions to sulfur in food! It may be very helpful for others who have similar issues.
          Debbie

  3. I have the CBS C699T +/+ which means you are more prone to upregulation which will cause elevated sulfur and ammonia according to the 23 and me test It also states to avoid/reduce sulfur as this will contribute to anxiety. I also am in doubt about this, as I find it impossible to be on such a restricitive diet. I am doing Amy Yasko’s protocol for CBS enzyme support, but unable to follow the diet. Can I still get better with the supplements w/o being on a low-sulfur diet?

    • Hi Sandra,
      Thanks for reading and commenting.
      The whole point of my article (which I may not have made clear enough) is that there doesn’t seem to be any research at all backing up the claims that everyone with the CBS C699T variant needs to be on a restrictive diet. Half the population carries that variant — and most thrive without a restrictive diet.
      Debbie

  4. Damn-this CBS gene is really putting a monkey wrench in things for me. I’m just learning about all this genetic mutations and I cannot do anything because I’m worried about this cbs gene. I’m homozygous CBS rs1801181 from lifehacker. I have mast cell activation with flair-ups of fibromyalgia and chronic fatigue. I tried taking a l-gluthione (sp) and I felt that it made my fibromyalgia symptoms flair up. So now I’m worried about having this sulfer problem. It’s so confusing as from what I read my snp shouldn’t have any affect??? Any clarification from anyone to help shed some light would be great!!

    • Hi Rose,
      I was right there with you when first reading about the methylation cycle genes on various website, but after digging through all of the research on the common CBS variants, there is nothing that indicates that they have much of an impact. I’m sure there are people for whom sulfur can be a problem, but I really doubt that most people with the common CBS variants need to restrict sulfur in their diet.

      Have you seen this paper by Dr. Theoharides about the possible connection between hypothalamic mast cell activation and CFS? https://www.ncbi.nlm.nih.gov/pubmed/30076265

      Mast cell activation increases ROS — so it seems like glutathione should help to reduce the oxidative stress. But people with mast cell problems react strongly to a lot of things, as I’m sure you know!
      (For anyone reading this who wants more info on mast cells: https://www.geneticlifehacks.com/notes-about-histamine-and-mast-cells/ )

      Just a thought – have you also checked to make sure you don’t have any of the Familial Mediterranean Fever mutations? It is an autoinflammatory disease that is sometimes misdiagnosed as fibromyalgia.
      Debbie

  5. Hi, I’m homozygous for CBS c699t, and I’m quite healthy, but with a few chronic symptoms – bouts of insomnia, tendency to anxiety, low energy, a bit overweight, reactive hypoglycemia, rhinitis in the morning, susceptibility to colds. I’ve occasionally had severe sneezing fits after white wine. I’m always looking for diet changes to help make my energy levels and well-being more consistent throughout the year. I have mostly cut out eggs, brassicas and pulses, and I no longer need to sneeze and blow my nose for the first two hours of the day I can drink a little wine without sneezing. I sneezed a lot after egg on toast a few months ago. So, while I am interested that current research has not linked the cbs mutations to ill health, I will not be adding eggs and cabbage to my diet any time soon.
    Also, while I am very pleased to breathe clearly for more of the day, it was the idea that I was building up ammonia in the body which scared me into taking action. I sometimes take L-ornithine at night (supposed to detox ammonia, recommended on Dr Jockers’ site) and it often helps me to sleep much more deeply.
    One last thing, I can’t get my head around Dr Jockers’ diet plan for cbs – has anyone ever managed to eat low carb, low protein and high fat?
    Thank you for your article and opportunity to contribute.

    • Hi Selina,
      Thanks for posting your experience with cutting out high sulfur foods. I’m sure that others will find it interesting to see how cutting out eggs and cruciferous veggies has helped you.
      Eggs are actually one of the top foods for allergies or food sensitivities. If they are making your nose run for a couple of hours after eating them, you may want to look into getting allergy testing done for eggs.
      Thanks for reading!
      Debbie

  6. I’ve struggled with difficult to diagnose issues which resulted in mild anhedonia, a lack of focus, and low energy levels. I had several other strange symptom, including sleep which wasn’t restful, random bouts of intense sleepiness after protein, occasional rashes on my face and body, and extremely cold hands and feet. After trying to tie all of it, it’s all come back to ammonia. High ammonia from an average diet has caused a BH4 deficiency which results in low nitric oxide. While I never wake up sweaty, it appears that small amounts of ammonia are excreted through my skin, which is why I get the rashes and why my sleep isn’t restful – my body continues to struggle to detox the overflow of ammonia after I awake. And the intense sleepiness comes from additional ammonia load from protein, which leads to an emergency flush of the brain to get rid of the excess ammonia in the brain (I found a study demonstrating this in mice). Showering twice a day instead of once has been helpful and reducing my protein intake has also helped.

    The problem is that my C699T gene is heterozygous which should not result in CBS upregulation, if indeed that is a thing (understood the point of the article that evidence is lacking). But if CBS upregulation isn’t the cause of the excessive ammonia production, then what could it be? It’s gotta be something in the transsulfuration pathway, but I’m not sure what.

    • Hi Daniel –
      Keep in mind that I’m not a doctor :-) But perhaps I can give you a couple of ideas to investigate…

      First, have you done a lab test to see if you really do have high ammonia? You could get a plasma ammonia test done after eating a meal high in protein. Along with that, you should probably get the standard panel called a Comprehensive Metabolic Panel to make sure that your liver markers are good. The most common cause of high ammonia is liver problems. UltaLabTests has the ammonia panel for $44 and CMP for $22 – but check around since all the online lab companies run sales and coupons pretty often.

      If your ammonia is high and your liver is fine, then try a low sulfur diet to see if that helps. There are other genetic variants in the transsulfuration pathway.

      If it isn’t ammonia, then the first thing that jumps to mind for me with restless sleep, lack of focus, periodic rashes is histamine intolerance or something going on with mast cells. Histamine acts on the histamine receptors in the brain to wake us up each morning. (That’s why older antihistamines, like Benadryl, make you sleepy.) When your histamine levels are too high, you can end up with poor sleep and hives / itchy rashes that come and go.

      Hope that something here helps you figure out the root cause of your problems. Good sleep is sooooo important for your overall health.
      Debbie

Leave a Reply

Your email address will not be published. Required fields are marked *