Methylation Inhibited by Candida’s Toxin

Repairing the digestive system and optimizing the flora should be one of the first steps in correcting methylation deficiency.

There are countless reasons for this; however, the focus here is the relation between methionine synthase and acetylaldehyde.

One must first understand what methionine synthase is and why it is important.

Methionine synthase: What is it?
The critical enzyme which utilizes the substrate produced by the MTHFR enzyme, 5-methyltetrahydrofolate, along with the cofactor, methylcobalamin.

Methionine synthase: Purpose?
The purpose of methionine synthase is two fold:

  1. converting homocyteine into methionine.
  2. converting 5-methyltetrahydrofolate to tetrahydrofolate which is then used to make other forms of folate which are needed to produce and repair DNA

Methionine synthase: How does it work?
By donating a methyl group to homocysteine from 5-methyltetrahydrofolate. Methylated homocysteine becomes methionine and since 5-methyltetrahydrofolate donated its methyl group, it now becomes tetradhydrofolate.

Tetrahydrofolate proceeds down the folate pathway to produce nucleotide bases which are used for DNA repair and production.

This process can be limited in those with MTHFR mutations because those with MTHFR mutations have a limited ability to produce 5-methyltetrahydrofolate.

As you can see from the image above, if methionine synthase does not have 5-methyltetrahydrofolate or methylcobalamin available, it cannot function.

If methionine synthase is limited in function, elevated homocysteine is a likely result along with reduced folate levels.

This limitation may be bypassed by supplementing with vitamin B6, methylfolate, methylcobalamin and betaine.

This works quite well typically but there may be other aspects which must be addressed in order to optimize the function of methionine synthase.

Enzymes do not work well if they:

  1. lack the active substrate such as methylfolate
  2. lack cofactors such as methylcobalamin
  3. are exposed to inhibiting compounds such as heavy metals, solvents, chemicals, toxins

Points one and two have been addressed.

Point three has not yet.

Methionine synthase has a few potent inhibiting compounds and one is produced from Candida

Candida albicans produces a toxic byproduct called acetylaldehyde.[1]

Research cites:
“Acetaldehyde-induced inhibition of liver methionine synthase activity is thus proposed as the most likely explanation of the reported in vivo effect of ethanol upon methionine synthase.” [2]

Acetylaldehyde is also a byproduct of ethanol.

Let’s make this very clear.

What are the major symptoms of a hangover?

  1. headache
  2. foggy thinking
  3. irritability and/or depression
  4. fatigue
  5. soreness
  6. sensitivity

What are the major symptoms of yeast overgrowth?

  1. headache
  2. foggy thinking
  3. irritability and/or depression
  4. fatigue
  5. soreness
  6. sensitivity

What are some major symptoms of reduced methylation?

  1. headache
  2. foggy thinking
  3. irritability and/or depression
  4. fatigue
  5. soreness
  6. sensitivity

When approaching anyone with a MTHFR or methylation defect, it is critical to take a thorough history and examine the digestive system first.

Commonly, when I work with individuals experiencing MTHFR or methylation defects, I ask:

  • History of antibiotic use in the last 5 yrs?
  • Steroid use?
  • Flagyl?
  • Take a potent multistrain probiotic?
  • Digestive symptoms? Constipation, diarrhea, IBS, etc?
  • Itchy anus?
  • Lichen planus? Leukoplakia?
  • White tongue coating?
  • Desire for sweets?
  • Recurrent vaginal infections?
  • Nail fungus?
  • Weak immunity?
  • Fatigue level?
  •  Cloudy thinking?

These are often present in those with yeast overgrowth.

You now know that acetylaldehyde inhibits methionine synthase and now you must do something about it.

Recommendations for reducing yeast overgrowth (and eliminating an inhibitor of methionine synthase):

  1. Eliminate soda, sugars and simple carbohydrates
  2. Support the immune system with selenium, zinc, vitamin C, vitamin A, vitamin D, vitamin E
  3. Reduce the reproductive ability of candida albicans with biotin and saccharomyces boulardii
  4. Reduce the production of acetylaldehyde by using oral xylitol products
  5. Support beneficial bacteria growth by supplementing with a potent multistrain probiotic.
  6. Utilize antifungal herbs and nutrients to eliminate yeast.
  7. Support elimination of acetylaldehyde with molybdenum, vitamin C, NAC, glutathione
  8. Improve intestinal motility with chia seeds, hydration, magnesium and reducing intake of dehydrated foods
  9. Eat meals with quality protein and vegetables.
  10. Eliminate biofilm with specific enzymes to eliminate recurrent yeast overgrowth
  11. Support methylation with methylcobalamin and l-5-methylfolate

Find many of the above recommendations here – in the Yeast and Candida Overgrowth section.

NOTE:
Given the complexity of the topic of methylation, this is one consideration out of many. There are many variations on how one must approach elimination of candida overgrowth depending on their genetics, lifestyle, age and current symptomatic picture.

The point here is to educate you that methylation is more than just genetics and vitamins – it is also significantly affected by your internal environment.

UPDATE on Sept 19. 2013: The writer over at Magnesium Advocacy Group made an excellent point about the need to support acetylaldehyde. While I mentioned acetylaldehyde inhibited methionine synthase, in my haste, I did not tell you how to eliminate the acetylaldehyde – which – sadly – is a mistake. I was so excited about the connection between methylation and yeast that I forgot to tell you how to mend it. Stupid right?

Read this article on how magnesium is essential to elimination of acetylaldehyde – keep in mind that magnesium is not the only nutrient needed to support acetylaledyde elimination but it is a big player especially since many of us are deficient in it.

 

References:

  1. http://www.ncbi.nlm.nih.gov/pubmed/22909057
  2. http://www.ncbi.nlm.nih.gov/pubmed/9590515
  3. http://www.ncbi.nlm.nih.gov/pubmed/21114016

Further Reading:
Cobalamin-Dependent Methionine-Synthase

 

 

 

 

 

 

 

 

 

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22 Responses to “Methylation Inhibited by Candida’s Toxin”

  1. Allie September 8, 2012 at 3:58 am # Reply

    Another very interesting article, thank you. Do I understand that drinking alcohol will therefore also inhibit the methylation process? (I’m homo C677T.) I very rarely drink alcohol, because even one glass of wine is likely to leave me feeling all of the above ‘hangover’ symptoms almost straight away, plus a bad night’s sleep and still groggy next morning. Recent candida tests proved negative, so not a part of the picture for me personally.

    PS amongst the questions you ask, above: is that desire for sweats as in sauna – or sweets as in sugary things?

    • Dr Ben September 8, 2012 at 3:44 pm # Reply

      Allie –

      Yes – alcohol does inhibit the methylation process.

      Wine is not only alcohol but sulfites. You likely are deficient in molybdenum.

      I’ve edited my typo – it is a desire for sweets (typing too quickly ;) )

      • Allie September 9, 2012 at 2:47 am # Reply

        Thank you, further enlightenment dawns! An occasional gin and tonic in the evening is usually ok – I thought it was because I had eaten beforehand, whereas wine tends to go with or even before the meal, but maybe it is the sulfites instead. One of these days I will pluck up the courage to try the organic preservative free bottle I bought recently. I live in a landscape of vines, on the doorstep of one of the world’s great wine regions.

        Molybdenum was very low on hair tests, as were many minerals due to mercury toxicity, but I have recently had my amalgams removed so hopefully some of that will come right. There is molybdenum in one of my supplements which should help.

        It’s a fascinating journey, I love it every time another piece falls into place :)

  2. Helen Janneson Bense September 10, 2012 at 3:44 am # Reply

    Awesome article! Thanks :)

  3. Kimberly September 25, 2012 at 5:42 pm # Reply

    I know you’ve chimed in before on “die-off”, but I know of those on GAPS that have had worsening of symptoms and still do after several months…just from introducing the diet. Myself, just starting Paleo this week, after anti-Candida supplements for 2 weeks have worsened to extreme anxiety/loss of sleep/panic/fog…I just introduced your Biotin at lunch and wanted to buy your Saccharomyces boulardi. Is Molydenum essential?
    As you know, my “allergy test” showed Sulfur and Vit C. So, I’m concerned with using NAC or Vit C…but am more concerned with healing and helping “die-off” symptoms that are intolerable.
    My Q- If you have severe reaction to detoxing or killing candida…does that mean it’s not clearing these out of your body but just moving them around((harmful) or is it working and if you can push thru it will pass?
    Thanks!

    • Gina July 29, 2013 at 11:35 pm # Reply

      Hi Kimberly,

      I was reading your comment/question and I could relate to the candida “die off ” symptoms that were intolerable. I did a 2 week kit from advanced naturals and I thought I was going to die from the anxiety and depression. I’m just wondering how things went for you. I took a heavy metals test and scored high in lead and mercury. I have not taken the mthfr test yet but that is my next step. Any imput on your situation might clarify things in my own situation.

      Thanks

      Gina

  4. Suzanne October 2, 2012 at 6:08 am # Reply

    Hi Dr. Ben,

    Diet-wise, it looks like the recommendations are almost the same for dealing with candida and for dealing with black mold illness. Is there any information you would add for those of us dealing with mold instead of candida?

    Thanks,
    Suzanne (MTHFR 677T +/+ with Lyme Disease and a severe black mold infection)

  5. Jess pisani June 14, 2013 at 11:17 am # Reply

    This should be called the mother fucker gene. I hear what your saying about the alchol. I call it “skin hurty”! Mine gets so bad I cannot stand any impact like running/ walking or clothes around my waist. I’m now on a treatment plan taking folinic acid, ashwaganda and b12. Keen to beat the mthfr mother fucker

  6. Sally August 1, 2013 at 1:51 pm # Reply

    Dr Ben, can u help solve this mystery that stumped my docs?

    My stool test shows 4+ yeast/fungus overgrowth and my oat and nutraeval all have high yeast markers (i have other dysbiosis too… Klebsiella pneumoniae, mycoplasma pneumoniae, parasite, and mold toxicity)

    My nutraeval showed that my levels of biotin were high, same with molybdenum, which is odd for having yeast overgrowth bc usually those levels are low

    Also, my methionine is really high at 143 (30-82), same with cysteine, glutamic acid, but low taurine

    Any insight into this? My doctor even called Genova lab and the doctor there had no idea. Why is my methionine so high, yet biotin low with high yeast? What should I do?

    Thanks so much

    • M Stan October 30, 2013 at 12:29 pm # Reply

      Biotin was low or high? You mentioned both in your post. There’s evidence that candida albicans utilizes (eats) biotin, and that biotin helps it grow, unfortunately.
      A study called “GROWTH PROMOTING EFFECT OF SOME BIOTIN ANALOGUES FOR CANDIDA ALBICANS”.

      People with candida are stuck – we need b vitamins, yet taking them (some of them at least) fuels candida growth. Some try using the b’s sublingually and spitting out the saliva, rinsing mouth, after the time period of allowing it to reach the bloodstream, in hopes of keeping the b’s out of the gut. Not sure if that works.
      Hope this helps.

      • Sally October 30, 2013 at 7:59 pm # Reply

        Sorry, I meant biotin is high as well…. Its usually low in people with yeast overgrowth and supplementing with Biotin is often helpful

        Any idea why my methionine is so high? I don’t eat meat. I have mthfr a1298c

  7. Lisa smelik October 24, 2013 at 1:05 pm # Reply

    Hi Dr. Lynch, I was tested and I have two copies of the A1298C mutation. I also was diagnosed previously with Hashimottos, celiac, and Pernious anemia. Just wondering which supplements I should take? I was going to order the ones for yeast overgrowth as a start but not sure. I am on B 12 injections 1,000cc/ml methylcobalamin ,selenium 200mcg and Nature Throid 1grain. Was taking lose dose liquid iodine but started feeling bad so stopped. Not sure if iodine is a good idea. Would appreciate any thoughts and guidance? I do have gut issues ( bloating constipation achy)

    Thank you so much for any advise!

    Lisa

  8. Rana October 28, 2013 at 8:06 am # Reply

    Hi Dr B. Which enzyme you meant to eliminate biofilm?

    Thank you

  9. Kim December 1, 2013 at 3:50 am # Reply

    If you take a peek at the Wikipedia page on aldehyde dehydrogenase you will see that it needs not only magnesium, but NAD(P)+, or niacin, to function. If you take magnesium, but not niacin or niacinamide, then that will become the limiting factor.

    The breakdown of histamine also creates an acetaldehyde, so candida is not the only contributor to this problem, but histamine producing gut bacteria. The buildup of acetaldehyde due to to lack of niacin and magnesium during the breakdown of histamine by the enzyme DAO, will cause a negative feedback loop inhibiting DAO (see http://ajcn.nutrition.org/content/85/5/1185.full) and causing SAMe to be depleted in order to get rid of the histamine through the enzyme histamine N-methyltransferase.

    I thought that my son’s problems were caused by candida, he even tested positive for candida, but he had absolutely zero die off symptoms from nystatin and it turned out that his problems were being caused by histamine producing bacteria, which also lead to acetaldehyde.

    We find in our personal experience in our family that taking large doses of niacin (with magnesium, B6, vitamin C, B12, folate and a good multivitamin) frees the methylation cycle to produce the amount of SAMe that you need and it appears that degrading niacin is a low priority job and all the other more important things get done and health is restored by adding the niacin (or niacinamide for no flush) to the protocol that we couldn’t achieve without it.

    • Dr Lynch December 3, 2013 at 7:46 am # Reply

      Excellent, Kim.

      Thank you for sharing. I will review this article.

      • Dr Lynch December 3, 2013 at 7:47 am # Reply

        Actually – I’ve seen this one already – it’s an excellent one – one of the best actually on histamine.

      • Kim December 3, 2013 at 4:08 pm # Reply

        Thank you Dr. Ben.

        I am happy to report that my son who has had schizophrenia for 10 years is responding to this protocol. When he first got sick I took him to an orthomolecular doctor who had him on all of these vitamins, except for magnesium. He tested rather high in magnesium, but I now think that was because he was low in B6, (I still have the test results, which I saved) which created a bottleneck at the DAO level, one level above the acetaldehyde level that uses the magnesium, so it wasn’t draining his magnesium yet. Later he did take B6. The protocol didn’t work but while he was still taking the vitamins, we moved to a new house that had a water neutralizer using magnesium oxide and after a couple of months he mysteriously got well, and stayed well for several months.

        Unfortunately, I didn’t realize that he had gotten well because of the magnesium in the water and he stopped taking the niacin and other vitamins and got sick again for these last 6 years, but now that we understand what was causing his schizophrenia and how the magnesium was an essential factor, he is getting well again.

        He has double mutations in the 2 well known COMT downregulations, which makes it hard for him to get rid of his dopamine unless he has plenty of SAMe all day and night and the histamine was draining his SAMe. Since his gut dysbiosis began 3 years before his schizophrenia, and his symptoms began exactly when he had mono, I believe that the mono somehow did something – switched a gene on or off – that caused his feedback mechanism that controls how much dopamine is made to no longer slow down his dopamine production when his dopamine levels were high, leading to schizophrenia. With the vitamin protocol his SAMe levels and niacin levels are high enough for enough of the day to overcome that problem. At least that is my theory about how it works.

        I think that the symptoms that an individual gets are dependent on their mutations. Our other son with dysbiosis gets fatigue and depression, which I think is caused largely by a mutation that makes his serotonin receptors accept histamine, because when I gave him 5-HTP (before I learned how to use the niacin, etc) it made him feel good, but I kept having to give him more and more until finally it wasn’t working any more.

        I think that when I gave him the 5HTP it raised his serotonin levels high enough so that more serotonin got into the receptors than histamine, but the high serotonin levels caused a feedback loop and his body kept making less and less serotonin, and it took several days with no 5-HTP for his serotonin production to recover. I suppose it is possible that his depression is from low SAMe, but I haven’t really seen what I would consider a good explanation for how low SAMe would cause depression and I think the explanations I have heard of have just been hypothesized because it is known that low SAMe levels are associated with depression but I wonder if the association isn’t just because the depression and the low SAMe are both caused by the same thing – histamine. That’s my current theory on that one. If anyone has more data about whether SAMe really increases the action of dopamine, serotonin and other neurotransmitters in the brain, I would be interested in seeing it. I think it might just as well be getting rid of the histamine that is interfering with the action of these neurotransmitters.

        Because of this, I think that when there is depression that people think is caused by candida, perhaps it is actually caused by histamine producing bacteria, because I am sure that acetaldehyde would not be accepted by serotonin receptors even if a person had a mutation, but since histamine is a neurotransmitter, it could be accepted by serotonin receptors in some people.

        Just so no one thinks that I think all depression is caused by histamine, I think that there are other causes of depression that have nothing to do with histamine, such as low BH4 from the MTHFR 1298 mutation or other mutations, which would make it harder to make serotonin and dopamine. The histamine type depression can be mild to very severe and does NOT respond to sunlight in our experience.

        • Dr Lynch December 3, 2013 at 11:10 pm # Reply

          Hi Kim –

          Thanks for the detailed comment – will review when I’ve a moment.

          I wanted to clarify something really fast –

          You stated this
          “such as low BH4 from the MTHFR 1298 mutation”

          I want to correct this and state the people can have low BH4 from MTHFR C677T as well – and even more so.

          BH4 has to do with methylfolate levels – and there is no forward and backward reaction for MTHFR. That said, those with A1298C and C677T both need methylfolate in order to support BH4 recycling. However, those with C677T may need more methylfolate than those with A1298C as the C677T MTHFR variant is more downregulated than 1298.

          • Kim December 4, 2013 at 12:03 am #

            OK, I was under the impression that C677T didn’t affect BH4 levels, but I was just trying to make the point that although I have a son who gets depression from histamine, there are other things that can cause depression.

            Quite a few of my statements are just my personal theories that I have from studying and from my experience with my sons. I hope I made that clear enough. I don’t want anyone to think that they have been proven by double blind trials or anything like that.

            It’s just that every discovery starts with someone observing and making a hypothesis, and I wanted to share my ideas in case they might help someone else because I have had quite a bit of help from looking at what other people have posted online on various sites, including this one, and it has been so helpful, but I think I have stumbled onto something that no one else has made the connection to before (fluctuating histamine creating chronic low SAMe and the connection to the orthomolecular treatments which no one ever really knew why they worked), and if I share it then other people can take it farther and more and more people can benefit.

      • Kim January 10, 2014 at 9:50 pm # Reply

        I would like to share what I have learned since my last post. My son who has had schizophrenia for 10 years has now been off medication and doing great for almost 6 weeks using these vitamins to support the pathways that get rid of acetaldehyde (because dopamine also creates an acetaldehyde in its break down pathway) and my son who has had depression is doing much better now that we finally figured out that B5 (to make coenzyme A) is needed in large amounts to get rid of acetaldehyde, in addition to magnesium and niacin and vitamin C. We also support the methylation pathway because the dopamine break down pathway requires SAMe and also in order to get rid of large amounts of acetaldehyde, we have found that you really have to have large amounts of niacin (or niacinamide).

        So the new addition is that we have learned through experience (because my son with depression would suddenly get worse about 20 minutes after eating something with fat in it, and coenzyme A is needed for fat metabolism, and because this stopped happening after I started giving him pantothenic acid in gram doses) that B5, which can be taken as pantethine or pantothenic acid, is needed to break down acetaldehyde in the body.

        I hope this is helpful to someone.

  10. Vince Sabio February 7, 2014 at 2:02 am # Reply

    Dr. Lynch,
    What are your opinions on Food Grade Hydrogen Peroxide for getting rid of Candida overgrowth? Some studies suggest that it helps to get rid of Candida..
    This is an amazing article. I wish more mainstream doctors are aware of this. My wife is suffering from this right now because of antibiotics and oral contraceptives. She suffered from Candida overgrowth and I think is still suffering from it systemically. I also think she is suffering from Adrenal Fatigue due to the infection, she is sensitive to indoor lights and some sounds. I did a pupil dilation test and found that her left pupil would pulsate while her right one would open up quickly, not dilate gradually under normal conditions. She recently had a MTHFR genotype test and she found out that she is A1298C Mutation Heterozygous.

    Apart from the suggestions you’ve made in this article, is there anything else we can do to help in her recovery?

    I look forward to your response. Thank you!

  11. Robin February 7, 2014 at 10:19 pm # Reply

    Hi Dr. Lynch,

    My naturopath gave me my results for my MTHFR blood draw, and it states that I am Hetero for A1298C. I’ve been feeling REALLY unwell for the past 9 months and I’m pretty sure it stemmed from when I took anti-biotics and started BC (which I had not used either for years), last May. I am no longer on BC, I stopped after 2 month’s use. My life has literally been put on hold. I am not able to do the things I loved before, like jogging trails, having spontaneous beach trips, going on walks around the lake…

    After I started getting unusual symptoms, I’ve seen 1 chiropractor, and 6 different doctors (PA or NP) at my local clinic (since I lost my job and did not have insurance)… I had to make do, and go to the nearest place that charged the least amount for not having insurance. This means sacrificing getting the best care. :(

    They all would tell me the same thing… Anxiety (You need anti-depressants). Which of course, I would decline. During the times I had been between doctors, I realized these symptoms could be due to yeast (I noticed some white on my tongue). One PA told me it was not thrush (he said “thrush was a band”), and I had no idea what I was talking about-the white coating was due to my intake of Vitamin C supplements and told me to get off the supplements for 1 month-which I did, and I think it made my symptoms worse!!! I did not go back to him. So when symptoms persisted, I visited another Doctor, I told him to run blood tests and that I noticed that I also had thrush on my tongue. He was pretty much the only one who acknowledged the white on my tongue, and prescribed me Nystatin mouth wash. To my regret, I did not take this due to not having funds, and I also read reviews online that it didn’t work for some (I probably just should’ve tried it anyway). So, I researched like a mad woman- started on the anti candida diet, and started taking anti-fungals, probiotics, milk thistle, you name it. But, I started to feel terrible. Probably due to die off. It was so bad, that I could not focus, or even walk at work and was fired in October. At that time, I had gone to a Naturopath and I told her my symptoms and showed her my tongue. She also said I most likely had yeast overgrowth. And that I had digestion issues- also have a large crack down the middle of my tongue. However, all she did was had me take blood tests for my thyroid and MTHFR. She did not run stool samples, because I had already done the blood tests for the others, and could not afford it the stool sample which was $340. I felt like she should’ve ran the stool sample FIRST before the thyroid and MTHFR tests. That way I could’ve known for sure what was going on with my digestion and start from there. Knowing that I had a yeast overgrowth, she should’ve given me a protocol that helped with my digestion. Not a treatment plan that recommended d-mannose, UNDA 243, or castor oil packs…. She honestly was of no help either. So, I just followed her protocol until I ran out of the supplements she recommended. I just don’t trust her judgement.

    Then about six months after trying all these different things to get rid of the thrush & candida (I know it was most likely candida because I had white long string rhizomes in my stool in October), I started to realize that I started having food sensitivities. I’m thinking the rhizomes caused me to have leaky gut. Unfortunately, I am still dealing with all these symptoms and white tongue, and it is 9 months later… with no relief or help from Doctors (conventional or alternative)!

    I wanted to know, is it safe to take H2o2 (food grade Hydrogen peroxide) to rid of the yeast? Also, I started taking l-glutamate to aide in healing my gut… is this going to make my methylation process worse because of amino acids?

    One more thing, I really do not feel that my Naturopath is knowledgeable enough in MTHFR diagnosis. The only advice she gave was to stay away from folate foods, no juicing, and to take methylcobalamin and activated charcoal. Is this the correct protocol for my defect? Or, should I just stick to healing my gut FIRST with the plan you have above in helping heal candida? I’m in desperate need to feel well again!! I need to be able to work again, without terrible symptoms. I need to pay bills and get more assistance/supplements.

    Any help, or response would be GREATLY appreciated!!!!! I’m serious, I have to get well soon, my health is at risk! Thank you!

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