Methylation for Dummies

If you’ve been giving yourself headaches by trying to understand diagrams like this, I think I can help you.

Here's a map of Reading. Which roundabout do you live near?
Stop looking at this image immediately. It will damage your eyes!

I spent years thinking I would never understand all this methylation stuff. I read online forums full of people who seemed to know what they were talking about, yet who made me hopelessly confused.

I wanted to understand it, because incorrect methylation can cause a wide range of serious medical conditions. It seems to be a particular problem among people with chronic Lyme disease, autism and CFS.

I suddenly realised I was approaching it the wrong way. I am a professional researcher. I had no excuse! After studying peer reviewed medical research, I feel ready to summarise this methylation business quite simply.

May I first make it absolutely clear that I am not a doctor or a scientist, this is not medical advice, and I am not taking any responsibility if I have got any of this wrong!

Let’s get started

Here’s my own methylation diagram:

Veronica methylation 1

You may notice I have removed a few details to make it clearer. Don’t worry, we’ll add them back as we go along.

 What is methylation for?

Methylation of toxic heavy metals, such as mercury and lead, makes them water soluble. This means they can be excreted out of the body in urine.

Parts of the DNA in living cells are methylated. In humans, 60% to 90% of the DNA needs to be methylated.
* Methylation makes embryonic stem cells differentiate irreversibly into different types of body tissue.
* It suppresses the expression of harmful stretches of DNA that have found their way into human DNA over time, such as endogenous retroviruses and mutations.
* Methylation is very important in neural development and it appears to be essential to long-term memory formation.
The Wikipedia article on DNA methylation gives more detail on this and cites a lot of original research sources.

Abnormal DNA methylation (hypermethylation and hypomethylation) is associated with cancer. In particular, a lower level of white blood cell DNA methylation is associated with many types of cancer. In most types of cancer there is hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or cancer-causing genes.

The cells lining blood vessels must be methylated to repair them, and undermethylation results in cardiovascular disease and hardened arteries. This condition has been correlated very closely in many medical research papers with high homocysteine.

Two types of white blood cells (monocytes and lymphocytes) must be methylated. Under-methylation in these cells leads to excessive blood clotting, causing thromboses and strokes. It also leads to impairment in the functionality of aspects of the immune system dependent on these cells, though more research is needed to understand this properly.

What happens when your body is not methylating efficiently?

You will accumulate abnormal levels of toxic heavy metals which are found in food, vaccinations and the environment.

You may very gradually develop signs of cardiovascular disease such as abnormal blood pressure, enlarged heart, orthostatic intolerance, chest pain or postural orthostatic tachycardia syndrome. However, many people have no indication of problems at all until they suffer a heart attack.

You may have blood which clots rapidly, and therefore develop thromboses or strokes.

You are likely to suffer memory impairment and may have a range of other neurological problems.

Children with autism have been found to have brain abnormalities which may derive from inadequate methylation of nerve cells during critical stages of brain development in early childhood. Folic acid (in the right form) is essential for methylation, and lack of folic acid in pregnant women has long been known to result in brain and spinal abnormalities such as spina bifida. After birth, this methylation process continues to be vital in the development of baby and toddler brains.

You will be at increased risk of cancer.

You may be susceptible to a wide range of chronic inflammatory illnesses, including some autoimmune conditions. This derives from inadequate methylation of monocytes and lymphocytes. So far a definite link has been established between under-methylation of these cells and the development of autoimmune diabetes and systemic lupus erythematosis.

You are likely to have a weakened immune system and be unable to sustain a strong immune defence against infections.

Why is it a cycle?

Most scientists talk simply about methylation, but Amy Yasko coined the term “methylation cycle.” She wanted to highlight the fact that homocysteine (bad) must be recycled, and a problem in the recycling of this harmful substance can result in a shortage of methionine (good), and thus problems in the rest of the methylation processes.

A good analogy would be traffic flowing around a roundabout. An obstacle in any of the roads leading off the roundabout, or anywhere on the roundabout, will results in traffic jams ALL AROUND the roundabout.

So far, so good: yet the roundabout she seems to have used as her model is this one!

I’m sure I’ve got some dimethylglycine tablets to help me get through this, I just can’t find them…..

What happens when you don’t recycle homocysteine back to methionine?

You can see from my diagram above that the methylation cycle has two halves.

One part (pink) methylates the things listed above. To do so it starts with methionine (an amino acid which you get from the protein foods you eat) and, once it has done all this methylating, it has given away its methyl group molecules, and you end up with homocysteine – a different type of amino acid.

The second part of the methylation cycle (blue) recycles this homocysteine back to methionine by adding methyl group molecules back onto it.

High homocysteine levels mean that somewhere in this recycling half of the methylation cycle, something is not working well. You may have genetic polymorphisms that mean you produce less than adequate amounts of the enzymes needed, you may have a deficiency in one or more of the nutrients those enzymes need to do their jobs, or you may have other factors that are suppressing production of those enzymes (this is what people mean when they talk about altered gene expression).

The best article on the web about what happens when you have too much homocysteine is on the Life Extension Foundation website. It summarises a large array of peer reviewed medical research, all of which is cited in the bibliography. I strongly recommend this article, which is so clearly written it is a joy to read.

How does the body change homocysteine to methionine and vice versa?

Now we can add a little more detail to our diagram.

Veronica methylation 2

Enzymes that methylate DNA, heavy metals etc

N.B. This is not a complete list, just an introduction to some of the more thoroughly researched polymorphisms.

MTRR = methionine synthase reductase
This changes hydroxycobalamin (= hydroxy B12) into methylcobalamin (= methyl B12) and, in so doing, it also changes methionine into homocysteine as a by-product.
Vitamin B12 which has been methylated in this way can be used for methylating DNA, toxic metals etc. This process changes it back into hydroxy-B12. It can be recycled infinitely.

COMT = catechol-O-methyltransferase
This carries out part of the process of breaking down certain neurotransmitters and catecholamines, including dopamine, epinephrine (= adrenaline) and norepinephrine (= noradrenaline). These neurotransmitters are essentially what create much of your personality, as they create your mood and emotions, inhibition of behaviours and ability to control the temper, and planning, short-term memory and abstract thinking.
People with a COMT polymorphism are slower than average at breaking down these neurotransmitters.
Normally they are balanced. Adrenaline, for example, causes a rush of excitement and stimulation to deal with a crisis, known as the “fight or flight” response. Dopamine, on the other hand, brings about the relaxed, warm fussy feeling people enjoy after a good, hard session of exercise: the word “dopamine” is derived from the same linguistic root as “dopey”. One is never supposed to have high levels of both of these neurotransmitters at the same time.
Imagine a child at school with a COMT polymorphism which makes him slow at clearing these substances out. He is full of dopamine, so he has immense difficulty concentrating and he appears to be making no effort. His teacher tells him off, frightening him and provoking a major adrenaline rush. Now the child is full of both adrenaline and dopamine, to he feels tired and wired both at once.
The commonest symptom of both children and adults with this problem is mood swings and extreme irritability.

Enzymes which recycle homocysteine back to methionine

N.B. This is not a complete list, just an introduction to some of the more thoroughly researched polymorphisms.

DHFR = dihydrofolate reductase
This changes reduces dihydrofolic acid into tetrahydrofolic acid. These are both forms of folic acid.
The form of folic acid (vitamin B9) from vitamin supplements, is called pteroyl-L-glutamic acid. I have read some articles claiming it is identical to the form found in foods, and other claims that this form is very rare in foods and that dihydrofolic acid is the “natural” form usually found in food. Both of these claims have been made in peer-reviewed medical literature and I have no idea which is actually correct – I think it is simply a matter of opinion. 

SHMT = serine hydroxymethyltransferase
This changes tetrahydrofolic acid into another intermediate substance called 5,10-methylene THF.

MTHFR = Methylenetetrahydrofolate reductase
This changes 5,10-methylene THF into the ready-to-use form of folic acid, called levomefolic acid, or 5-methyl tetrahydrofolate, or 5-methyl THF, or 5-methyl folate. These names do not exactly roll off the tongue, so when bigpharma company Merck created this useful version in tablet form, they invented the trademark name Metafolin, which is widely used in online discussions of methylation by laymen (or laywomen) like me. It is licensed to various nutrient producers so you can find a range of different brands.

BHMT = betaine homocysteine methyltransferase
This changes homocysteine into methionine.
It takes trimethylglycine (=betaine) + homocysteine, and produces dimethylglycine + methionine. Most research on this enzyme comes from Amy Yasko’s clinical observations, not from peer reviewed medical research.

MTR = 5-methyltetrahydrofolate-homocysteine methyltransferase
This converts homocysteine back to methionine as well.
It takes 5-methyl folate (metafolin) with homocysteine, and produces methionine and tetrahydrofolate (THF) which is “ordinary” (inactive) folic acid.
According to Amy Yasko, the MTR polymorphism is an upregulation, meaning the enzyme is over-active and uses up too much methyl B12. I cannot find any peer-reviewed medical research which verifies this.

Other enzymes

CBS = cystathionine beta synthase
This is something like a major road off the methylation cycle “roundabout.” Instead of recycling homocysteine to methionine, it turns it into cystathionine. Cystathionine is converted in sequence by various enzymes and this process is called the trans-sulfuration pathway.

Various parts of the body need to be sulfated, but this is a topic for a separate blog post.
Polymorphisms in enzymes in this pathway will cause intolerances to sulfites, sulfates or other forms of sulfur.

If this trans-sulfuration pathway is not working efficiently, you will also accumulate excess amounts of ammonia, hydrogen sulfide and alpha-ketoglutarate, which Amy Yasko and associates say leads to excitotoxicity – manifested by stimming in autistic children and a feeling of being “tired but wired” in adults. This is an anecdotal clinical observation rather than the conclusion of scientific research.

What can make the methylation cycle go wrong?

1. Polymorphisms that reduce the quantity or effectiveness of any enzyme involved in the cycle

2. A deficiency in any of the nutrients needed by these enzymes

3. A reduction in gene expression, which could be caused by drugs, infections or other environmental factors. This is an area of research and so far not much is known about this in relation specifically to methylation. It is known so far that antibiotics of the tetracycline-doxycycline-minocycline-lymecycline family alter gene expression extensively and consistently.

How common are methylation cycle polymorphisms?

A heterozygous MTHFR polymorphism is found in 30% of the population worldwide, and the more severe homozygous  form (homozygous means you inherited the inferior gene from both parents, not just one) is found in 10%. This particular polymorphism is so far the one most intensively studied in the scientific community, as it directly causes a build up of homocysteine which has been proven to be the cause of hardened arteries and heart disease.

MTR polymorphisms are much rarer. A homozygous MTR A2756G polymorphism affects fewer than 1% of the population, for example.

There are scattered articles providing information on the prevalence of the other polymorphisms, but often they study a specific ethnic group, or a study population too small to extrapolate the data to the population at large. It does seem, however, that some of these polymorphisms are far from rare.

Why are methylation polymorhisms such a problem for some people?

The key factor for people with discernible methylation related symptoms appears to be the specific combination of polymorphisms they have. Most of the groups of enzymes involved in the methylation cycle do a job can also be done by a different set of enzymes – a plan B. The really important processes sometimes have a plan C as well. Someone who has a polymorphism in a plan A enzyme, another in the plan B enzyme and possibly one in plan C will logically be likely to suffer adverse effects. Someone who has a scattering of polymorphisms affecting different systems, but who can reliably fall back on plan B, may never suffer symptoms.

The sheer number of polymorphisms is also bound to be an important factor. As an example, my rudely healthy husband has two polymorphisms (vitamin D receptor and MTHFR) whereas I, with chronic Lyme disease (and CFS if you believe some of my past doctors), have 4 homozygous ones and 6 heterozygous ones.

Why is methylation important in Lyme disease, autism and CFS?

The symptoms of impaired methylation described above are common, perhaps universal, in people with autism, CFS and Lyme disease. People with these conditions who can pay for genetic testing always seem to find a range of genetic polymorphisms which will reduce the rate at which they produce enzymes that form the methylation cycle. So far there has been no population-wide research that has compared the rate of these polymorphisms in patients with these illnesses against the rate of polymorphisms in the healthy population.

Most people with Lyme disease, for example, felt perfectly fine before catching Lyme disease yet already had all these polymorphisms. It is possible that the Lyme disease itself triggered a change in gene expression which took their adequate (but less than ideal) production levels of these enzymes down below the “adequate” threshold.

How can you tell how well or badly you are methylating?

A blood test of homocysteine levels will highlight problems with recycling methionine back to homocysteine. If you start taking nutrients to help your methylating processes work better, you can repeat the test to monitor progress. Read the Life Extension Foundation article which discusses different levels of homocysteine.

A DNA test performed by 23andme (or some other companies) and then analysed by Genetic Genie will indicate if you have relevant DNA polymorphisms that will reduce your ability to make many of the enzymes which collectively form the methylation cycle.

Genova Diagnostics offers various test panels which monitor how your methylation processes are working. (I have no personal experience at all with this company.)

If you know of other tests that I have not mentioned here, please add a comment, and post a link if possible.

Finally: how to spot and avoid twaddle…

Crazy diagrams are often accompanied by comments which are poetic rather than scientific, such as

“Once long-closed metabolic pathways are reopened, the body may be unable to handle the accumulated toxins and will need detox support to deal with nasty symptoms.”

or “Trimethylglycine is the most powerful methyl donor and may be needed for those extreme under-methylators but beware, as it is very strong!”

The first comment is a surefire sign you are dealing with a quack. When something is helping your body, it does not make you feel worse before it makes you better. It just makes you better. Steer clear of snake oil!

The second comment comes from someone who just knows even less than I do about chemistry. Scientists do not talk about molecules being more or less “powerful”. That is an emotive word used by novelists and screenplay writers, not scientific researchers. Certain enzymes act upon certain substrates. They pull bits off molecules or stick bits on. That’s all. Trimethyglycine is a nutrient with three methyl groups on it, as oppoed to two or one. People make enzymes to pull one of them off. The end.

And by the way, some people have genetically impaired production of the enzyme needed to pull one methyl group off, which means it is not “powerful” for them, it is useless, and possibly a little bit harmful.

These are just examples, but the internet is full of writing about the methylation cycle which may have been science once, but has been retold and garbled into misinformation and nonsense. Be sceptical if you read anything that sounds sweeping and allegorical rather than scientific and specific.

I personally have issues with some other treatment approaches. Amy Yasko first realised people with autism apparently have all the symptoms of inadequate methylation, and she deserves great credit for that. The aspect of her therapy that I dislike is that she recommends not only the single nutrient you need to correct an enzymatic inadequacy, but a long list of different herbs and sometimes drugs as well. Why?

Taking herbs to improve the body’s methylation will not work, as these substances have no natural role to play in human biochemistry. Methylation is carried out by specific enzymes, each one using specific nutrients – it cannot be done in any other way.

…and how to find the truth

I started with peer-reviewed medical research published in reputable journals (excluding ones behind paywalls because I’m skint). I was surprised to find that some aspects of the methylation cycle, which are widely discussed among people whose lives are ruined by Lyme disease, autism or CFS, have absolutely no basis in objective scientific research at all – whereas others have been researched and verified very extensively indeed.

Then I moved on to analysing the evidence presented by Amy Yasko and her associates in the DAN (Defeat Autism Now) movement, reading as much as I could about their working theories based on clinical observation of their patients. Doctors usually let their personal bias affect their claims when they work this way, so information from this category has to be used more cautiously.

Sources and Further Reading

The best article on the web about what happens when you have too much homocysteine is on the Life Extension Foundation website. It summarises a large array of peer reviewed medical research, all of which is cited in the bibliography. It is highly readable and a very good place to start.

Wikigenes is a fantastic site which unifies masses of research on genes, enzymes etc. You can search any of the enzymes in this article, which will pull up a page of summarised research articles, with links to the full article.

Wikipedia article on methylation

Wikipedia article on DNA methylation

There are also Wikipedia articles on each of the enzymes listed in this article.

Amy Yasko’s treatment approach to methylation problems is explained in a free online book. She recommends a lot of tests and a very large amount of herbs as well as nutrients (an approach I personally disagree with. There is an argument that you get specific nutrients from herbs, but at what dosage? Why not take a measured nutritional supplement?).

The Heartfixer website explains a similar approach but gives a lot more scientific detail, and a therapy focused tightly on nutrients without additional substances (an approach I personally find preferable, and of course much cheaper!).

This article has links to lots of published research on DNA methylation.

A search on each enzyme in the SNPedia research database will produce a list of links to all the relevant peer-reviewed research on that enzyme available online free of charge. In the search box on this website you have to enter the abbreviated name (e.g. MTHFR) rather than the full name (methyl tetrahydrofolate reductase) – if you use the full name, it tells you there are no results.
This is the MTHFR page as an example. You have to click on the various SNPs (all possible known variants of the gene) to find the research specific to that variant.

This research article talks about some chronic inflammatory conditions related to abnormal methylation of monocytes and lymphocytes.

So far, this is the only actual peer-reviewed medical research paper I can find online about methylation impairments in autistic children:


59 thoughts on “Methylation for Dummies

  1. Thank you so much for breaking this down. Diagrams like the methylation one can be very intimidating!! I really appreciate your work!!


  2. Yes you did a great job thank you. As a Chiropractic physician working in this field for years now it is obvious to me that as you address the genetic issues with those required nutrients the impaired chemical cycles complete more properly. This can cause ‘upstream’ detox pathways to work more efficiently and if the ‘downstream’ pathways are not working well or the organs are not efficient you will get increased symptoms of detoxing. This is where a skilled practitioner can be very helpful using nutritional, herbal and natural detoxing knowledge to assist the body in the healing process. PS. I find that you are right in your statement that specific nutrients are most effective in compensating for the genetic SNP defects. Specific forms of B vitamins, etc. and especially specific minerals, often Molybdenum chelate and selenium chelate. My conclusion is that they must not be in our soils,thus the foods.

    Liked by 1 person

  3. Thank you, well said. Much better than I do, which is why I put your post on my blog, I hope you are ok with that. It is the first thing I ever reblogged (not sure of etiquette, WP seems to think it’s a compliment but it sure feels like grabbyhands). Best of health to you.

    Liked by 1 person

  4. What an amazing article. You are heroic to have done this. Have you come across research about how folic acid can block methyl folate receptors? I saw that on a Benjamin Lynch video (depression session series) but haven’t managed to get any further info. Very interesting tho, and may have wider implications. Love the blog. As an Anglo/US brought up in Rome, its hard not to be completely jealous/amazed at your skills living life in sicily. best Edward


    1. Growing up in Rome must have been fabulous – I am envious of that! 🙂 It took me three visits to the post office before I actually managed to send a small package to England today, after a week of trying!!!! So I think the only skill for life in Sicily is patience!!

      I’m glad you find this blog useful and yes, I did see that article. I assumed it was the case when I started taking ordinary folic acid and realised it was actively making me feel ill, as opposed to simply not helping.
      I haven’t seen that documentary but I read about it here:

      That page cites the following research, some of which may be online:

      3. Strum et al. “Enzymatic reduction and methylation of folate following pH-dependant, carrier-mediated transport in rat jejunum.” Biochim Biophys Acta 1979; 554, 249-257.
      4. Kelly et al. “Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements.” Am J Cliii Nutr 1997:65:1790-5.
      5. Colman, Green, Metz et al. “Prevention of folate deficiency by food fortification. Il. Absorption of folic acid from staple foods.” Am J Clin Nutr I 975; 28:459-64.
      6. Shils et al. “Modern Nutrition in Health and Disease, 9th ed”. Williams & Wilkins, Balt., 1999.


      1. That’s fantastic, thank you I’m interested partly because I wonder if it might not be part of a wider mechanism that applies to more vitamins and minerals as well.

        Can I try you on one more? IIRC Lynch said in a youtube that we will struggle to get enough B6 without eating grains. That really shook me up. I’ve been off grains for 6 months, and reached right for the Quinoia… but normal online sources suggest you get B6 from lots of foods. Do you have views on the relative merits of grain (non gluten) consumption for those of us with a past in or suffering from chronic auto immune or inflammatory issues?

        On a life note, If you succeeded to send a parcel in only 3 attempts, maybe that’s not so bad. I’ve been trying to close a dormant bank account here in london, and so far its taken 4 visits to the bank, multiple repeat requests, and no end in sight. Trying to telephone this branch was one of the most stressing experiences of the year. The Kafka virus is alive and well at HSBC.

        Then you’ve got lemon groves and Siracuse. Fra Angelico and Sciascia. Not to menation that if you were going to choose one spot on earth vegetables would love most to grow up in, it’s got to be Sicily (assuming of course that the usual suspects aren’t involved in weeding or pest control). My favourite daydream is to have an allotment on the slopes of Taormina. Though thinking about it, Sicily is really due for some well thought out natural reforestation. Too hot in summer without woods to take refuge in. best, Edward

        Liked by 2 people

      2. Hiya!
        That’s interesting about the vitamin B6 and grains issue.
        My son has a gluten-free diet planned by a nutritionist who used a computer programme to work out the amount of each nutrient the diet provided and there was definitely enough B6 in it, so I think it is probably not true about teh grains.
        My nutrition reference book by Henry Osiecki says 75% of the B6 is lost when flour is milled and that heating destroys another 30% to 45%. Other rich sources of B6 are cantalupe melons, avodadoes, bananas, legumes and lentils, walnuts salmon, tuna, sunflower seeds, peanuts and carrots.
        However, I eat all these and still have a B6 deficiency so I think there is an absorption problem, or else having chronic lyme means I need far more than an average, healthy person.

        Oh yes, UK banks! They sem like a misery till you try Italians banks – just the queueing is a misery even before you find they have paid your salary to another person because they typed your Codice Fiscale wrongly into their computer!!! (that really hapepned to me!)

        Currently my dream is to buy a lovely house near Siracusa, with some land around it, and live there with my export business selling top quality organic olive oil to the UK. Sigh!


  5. Yes, thanks for all this info. So many things to think over. I wonder the extent to which there’s a difference between how we metabolize a factory farmed banana or carrot, and one grown by a local farmer using organic fertilizer and no pesticides. I saw a study comparing the amount of antioxidant in US supermarket cinnamon being 1000% less than cinnamon grown wild in Norway. So a plasticated genetically modified banana might be more of a toxic load than a benefit.

    And if we have gut disfunction or hyper-permeability, those epithelial cells regrow every 4 days, so they may be asking for a lot of vitamins and nutrients. Is it possible that there might be something in the B6 molecules that makes something in the epithelial barrier tag a lot of them for rejection? Then there could be blockages in the vitamin transport pathways, before getting into cellular absorption. So many aspects that all need to work in tandem.

    What would be your basic advice for someone whose got CFS/ME? I’ve got a family member here with that issue, and we’re struggling to find a way forward.

    Love the dream. It’s not far from mine. Bad season for olive oil though. And I’d want to through in some citrus too, maybe pomegranates, and what about almond groves. But the scent of a citrus grove ihas to be one of the great sensory experiences.

    If you get your dream going I’ll def buy the oil and sell it in Portobello. There’s a lovely italian guy from Puglia selling good oil there now.

    best edward

    Liked by 1 person

    1. It’s so true about “artificial” fruit and veg possibly doing us as much harm as good.

      I tink the problem with limited absorption of nutrients is not a factor inherent in their structure (which is standard as far as I know) but in our ability to absorb them. Most nutrients need a transport factor made by our gut, which latches onto the nutrient molecule and pulls it into the blood stream and into the cell as needed. An intestine damaged by infection or whatever may make less of quite a few of these transport factors.

      I was diagnosed with CFS for years and my advice would be to view it as multi-infectious disease syndrome, and do all you can to identify the list of infectious diseases you have. that way instead of reading research into CFS, you can start reading research into these infections, which is much more specific CFS is a mixed bag of people with a varied assortment of infections that they cannot kick for reasons unknown, but knowing what you’re dealing with give you much more directed information on how to tackle them.
      The vast majority of people with CFS have Lyme disease, and other tick borne infections, so that is where to start. The Lyme test produces a lot of false negatives so you need to join a Lyme Group online to find a good lab in your area. Then you need to test for the main chronic viruses to see if they are dormant or flaring up, mainly HHV and EBV, also cytomegalovirus. Then there are other common chronic infections, mainly chlaymdia pneumonia and mycoplasma pneumonia.
      So, that is where I would start.

      I am so excited about this food importing idea. Sicily is so keen on organic farming, and of course organic farming works well here because everyone is doing it – if you’re one organic farm in the middle of a load of crop sprayers, every insect in half the country comes to eat your stuff! But if you’re all organic it produces great fruit and veg.


  6. Thanks, that’s really helpful. Once testing is done, does it make much difference to what happens, or are we still talking the usual diet and lifestyle changes (elimination diet, toxin reduction, figure out supplements, good sleep, lower stress, pace etc), or are there specific protocols for different aspects? I ask only because the person in question is currently reluctant to take tests, so if that remains the case, i’m hoping to steer them in the right direction anyway.

    Yes, organic farming is the future. I think culturally we have got this backwards. Its not that there’s normal farming and organic farming. I feel there’s traditional farming using natural processes, and toxic farming using poisons which produces toxic plasticated food. I read that in the US they are now allowing Agent Orange as well as Roundup to be sprayed on crops. One thing that worried me recently is that apparently the farmers in Puglia have been told by EU inspectors that they must cut down the mould infected trees at the stump, and then they can replant with GMO trees which will give ‘fruit’ in five years. The traditional way IIRC was to paint the trees with lime, and they would recover after two years or so.

    Re the structure of foods, I was referring to work by Aristo Vojdani (of Cyrex labs) who has an excellent youtube lecture on antigens and antibodies. If I understood correctly, toxins such as aflatoxin, pesticides, bpa plastics, food colourings, heavy metals and all sorts of garbage can actually bind to the food molecules so they change the molecular structure. Mercury in tuna is an obvious one, but aluminium leaching into soft drinks and BPA into starbucks coffee, or antibiotics into milk are other examples among millions.
    This means in the first place that the immune system will identify the molecule as toxic and react to it, but even worse, it could then learn and classify all future instances of a component of the specific food as toxic, and trigger immune reactions to it. So then we become intolerant. This could be part of the reason why gluten gliadin etc are causing problems for so many people. Not to mention that gluten and gliadin are also opening the tight junctions of the intestinal tract, which then allows these other toxins to enter the body. Then there’s molecular mimicry, where the immune system reacts to another food which shares some physical characteristics with one that our immune system is already reacting against. All this means that we need to be hyper vigilant about what we are eating and try to eliminate toxins as far as possible.

    So what I’d like to see is farms and food coops that video their entire production process and show us exactly what they are doing. Full disclosure. And distribution chains that don’t then process the food further, but protect it Then we need consumer education. I eat a lot of olive oil, but I don’t know enough on how to store it, how to identify if its gone rancid, how to avoid heating it too much, why that’s a potential issue etc etc. I feel we need a real tranformation or revolution in our food chains to stem this tidal wave of chronic and autoimmune conditions.

    best e

    Liked by 1 person

      1. I’ve asked about that test and one person said they got a false negativ and wasted 5 years getting worse before getting a positive from Igenex. The other person said they seemed sport on and were also very accurate in identifying co-infections as well.
        So, mixed views there.
        It is probably better to find a lyme specialist doctor and use whatever lab they recommend, perhaps.

        Liked by 1 person

      2. ‘I’ve asked about that test and one person said they got a false negativ and wasted 5 years getting worse before getting a positive from Igenex. The other person said they seemed sport on and were also very accurate in identifying co-infections as well.
        So, mixed views there.’

        Right. Happens a lot. It’s one of the risks of tests. If its a serious issue, one might be better off getting tests from two different labs. But that really ramps up the costs!

        Liked by 1 person

      3. Re the tests, its also worth bearing in mind that (at least according to wikipedia) ‘Blood tests are often negative in the early stages of the disease.[1] ‘ but i havent read the piece to discover what ‘early stages’ means.

        Liked by 1 person

      4. Early stages usually means first 6 weeks. Most docs make patients wait 6 weeks before testing.

        You’re not kidding about the cost!!! It costs hundreds of pounds just using one lab!

        I always use Infectolab in Germany, they are one of the best labs and most widely trusted. Arminlabs is a new and slightly cheapr one which uses exactly the same reagents – the head of Infectolabs is now running Arminlabs and so I think it may be the better one. They use three separate tests to look for borrelia in 3 different ways and have recently found a way to detect the cystic forms too – not sure if that’s commercially available yet.

        The other one people swear by is Igenex which looks for DNA fragments of Borrelia instead, this is ideal since you often have periods where borrelia has suppressed your immune system to the point where there are no detectible antibodies but Igenex will still find it anyway.


    1. That’s fascinating about the molecular modification of foods and how it coudl relate to allergies. it would make perfect sense of the rise in these medical problems, particularly in countries where we spray our food with so much toxic material.
      How to avoid it all? It’s so dangerous and so invasive.

      After a diagnosis of specific infections you can start to make sense of which infection is causing what symptom and choose what to deal with in a targeted way.
      For example, when I get a flare up of heart symtoms, sinusitis and allergies at the same tme, I know it is chlamydia pneumonia, and there are certain supplements I take to help my immune system work specifically against that, and if it gets really bad, I knowwhich antibiotics will help.
      Meanwhile at the moment my glands are all swollen and terribly painful, which I know is EBV, so I am on lots of Lysine and I have suspended all my methylation supplem,ents (B vitamins etc) because methylation helps that particular virus flare up.
      Wthout knowing which infections I have I would never have go to this point of unravelling the long and varying list of symptoms I am always battling with.

      Liked by 1 person

  7. Sorry to hear you’ve got symptoms. Still its really impressive how much you get done regardless. Re molecular mimicry, the recommended way to tackle it is to go on an elimination diet, or do a test (Cyrex array 10 is one of the most respected – but its going to be less reliable for lots of reasons). Then eat organic farmers market style veg and wash it carefully. And develop good toxin/platiscs/cleaning agent avoiding habits (like no starbucks, but that would not be a prob for you I guess).

    Have you ever tried an elimination diet? (Tom Malterre is good on that and has resources on his website, I do the Datis Kharrazian one from his book ‘Why isn’t my brain working’, which is a must read for chronic conditions IMO.).

    Im sure the toxic veg issue is much greater in the US/UK, and probably pretty low in Sicily. The advantage of the elimination diet is that if you do it consistently and thoroughly its the most reliable test of cross reactions. Having said that, IMO ramping up help to the microbiome through prebiotics and probiotics, as well as Vagus nerve and digestive support might mean that over time we loose cross reactivity or at least some minor intolerances. But that would probably be after at least a year of elimination diet, 80% organic veg diet, super high quality protein. Vojdani (and he’s got an interesting video presentation coming up at cyrex labs) says we should avoid fine ground flours in any case (like fine ground plantain or tapioca) let alone normal grains.

    Thanks re the rationale behind testing. That does make sense. Personally I think its hugely empowering to know. Also there are so many next generation tests coming out, and the quality is so much better. What I’d like to discover now for instance is the best practice in terms of minerals and vitamins. How to establish how much we personally need of each at any point in time, what our bioavailability and absorption capacity is, what the best source and kind is, and really how much there is in our food. Even the respected sources of estimates can be way out in my opinion. I bet an organic tesco carrot has 0 mcg of magnesium. We’re just not getting minerals and nutrients from foods unless the food chain contains natural organic fertilizers and is allowed go get fallow or rotated properly.


    1. I have done a full-on elimination diet several times to identify new foods that gave me problems. It turned out nearly all of them do!!!
      It was very useful to figure out the worst ones, though I have some metabolic problems that make me react badly to certain nutrients as well as allergens and toxins.
      As you say, the amount of nutrients varies a lot. I felt awful after eating 3 slices of (Sicilian) cantelupe melon recently because it has so much vitamin B6 in it!! I react to B vits by methylating much faster and this is unfortunately fuelling a major Epstein Barr relapse for me 😦
      I am lucky in Sicily as it is so easy to avoid most of the food additives that plague you in the UK/US and the veg are much more nutritious, you can see and taste it.


  8. Have you come across Christopher Shade? Just saw this video and very impressed…

    I’ve been taking a lot of the bitters/herbs that he recommends anyway, but its good to know the science behind them. The quintessential sea minerals are new to me. Def going to give them a try. best edward


  9. so thankful that you have made a difficult subject easier to understand, great breakdown and easy to follow.

    where does lyme treatment possibly sit with doxycycline, minocycline and tetracycline if they can alter gene expression extensively and consistently I think I read? and could this be happening with other antibiotics?


    1. I wish I knew the answer to that. I just have no idea. I do know know gene expèression gets altered by countless things, including what we eat, so it’s something quite hard to manipulate in a live human being in a controlled way I think.
      One thing I do know is that after 3 years of minocycline and other antibiotics I feel as if my body is permanently weakened and changed.


  10. BRAVO!!! After recently having a Los Angeles (CA) doctor spend over 15 minutes using the complicated diagram as a way to stroke her own ego, I laughed so hard when I saw your ‘Good / Bad’ diagram, I nearly peed myself 🙂


  11. Here is a question from apparently an ‘extreme’ dummie: “What does ” N.B.” mean at the start of some of your sentences? And, PS: Italy is grand!! We never lived there but were delighted to enjoy several weeks each year back before we got old. The Post Office is indeed, at least in the 90’s, a most harrowing experience. I recall how many times we stood in lines to mail something, only to get to the front of the line and have the window close up for ‘break’….or have to go to the end of an adjacent line because the window we were at did not have ‘tape’ but the window less than an arm length away did….but still we had to go to the end of the line. The biggest learning curve at the PO in Italy in the 90’s was the secret trick of knowing how to wrap, tie and secure the string in the little metal clip before the PO would accept your package. Ah! We do love Italy!!


  12. I’m interested in why you disagree with Ann Yasko’s approach of taking herbs…usually naturally occurring substances are absorbed better and contain nutrient combinations that see them more readily absorbed than single ingredient tablets. Can you explain?


    1. I fully support herbs as medicines. I take them myself. But problems in methylation lead to shortages of specific nutrients, not herbs. You cannot use herbs to replace vitamins, they’re not the same thing!

      Liked by 1 person

    2. We have found through our experience that each SNP requires specific forms of B vitamins and chelated minerals in specific dosages to function optimally. The problem with using herbs for this is that mineral and vitamin content can very dramatically. With our testing methods we can specifically find the nutrients and minerals need to up regulate each SNP in the methylation cycle for best results.

      Liked by 1 person

  13. Thanks for this! I needed to see how much everything really comes down to methionine just from a variety of different directions. I contracted Lyme while visiting the US when I was 20. When I was 28 and struggling with a myriad of health problems I was told by doctors that it was all in my head and that I only had antibodies to a previous infection. Now I am 38 and have two sons with autism who are completely nonverbal (ages 6 and 8). Apparently it is now in their heads as well :/. The key for us has been figuring out the cause of our very abnormally low cholesterol. I don’t have a report on our genetic polymorphisms but it would seem that we need to look at the BHMT pathway leading up to methionine because all of these missing pieces of choline, tmg, and methionine would result in low cholesterol. Already tried choline with them and it improved their ability to verbalized. B12 was not a good fit for us and besides everything I find on B12 deficiency shows that it would lead to high cholesterol. Some more of the “twaddle” I have encountered is that if a nutritional supplement is right it will lead to immediate and even dramatic results and should be given in mega doses. I intend to go low and slow because I think supporting this pathway for us will heal a liver destroyed by Lyme even if there aren’t immediate fireworks. Please keep sharing you insights for those of us who are seeking to help our kids!


    1. I totally agree about being slow and cautious. Especially with autistic kids who can’t give you their feedback about what they are feeling inside.
      I have built up to big doses of some nutrients but only after trying a little dose and building up gradually


  14. Thank you for your article, I have stumbled across this when researching and it made all the difference. I am also a Twin, I have a twin brother so we are fraternal. I have a dual mutation of MTHR (Homozygous Mutation C677T detected) and Factor V Leide N Mutation (negative) and the paperwork that my doctor gave me states results show that I have a methylation defect. The doctor who determined this is my Gyno as I went to get Bioidentiacal hormones due to so many symptoms I have been having – 46 year old female, no children. I had no Testosterone or Progesterone, and ran this gene testing to see if I had a clotting disorder as I did have a blood clot a few years ago after a minor knee scope surgery. While I do not have a clotting disorder, I left with a huge confusion over what is/was the real issue. They did do a low dose of hormone pellets, and also sent me home with $200 in “supplements” as follows: Methyl Folate Plus, Full Focus, Neuro-Immune Stabilizer, 81 mg of aspirin and 2g of fish oil (4 pills a day) – mercy. Understand I am a past gastric bypass full RNY patient out +15 years now and have always had issues with digestion and food, and until recently severe iron deficiency to the point I had to have Iron Injections by IV. When you illustrate in your article that the herbs are/cannot change our DNA – is that the same for these supplements? I have an issue with putting so many things in my body – I really don’t have any side effects other than the size of the fish oil but I have managed. I am not excited in any way to shell out 200$ a month on herbs/supplements. WIll these make the difference,I struggle to answer these questions and my doctor acts like it is not a negotiable issue….to the point I am ready to find another doctor as when I ask questions, she medically answers them, but I am fairly educated myself and want to “understand” what is functionally happening. Is it likely with twins that we both have the mutations, interestingly enough my twin did have Lyme Disease about 2 years ago and never had a recurrence, but other than that he has never had any ailments or health issues ever. I however have had cancer, Malignant Melanoma, Gastric Bypass, at one point elevated HBP, DVT, and general aching as I get older and issues with exhaustion/brain fog (seemingly called). Most curious on the supplements – do they matter, will they have an effect – or just may/may not curtail symptoms associated with the mutation/MTHR? I appreciate yours, and anyone else’s input. I understand the MTHR and write up you so greatly illustrated, I guess I am perplexed how at 46 this has never come up or been tested until menopause. Thank you for your time.


    1. The supplements that you listed sound like they are predominantly, if not all, nutrients rather than herbs. If they are the right ones, they most definitely should be able to help you. If you trust your practitioner to give you the right ones, I really would try to give them a chance.
      Given your gastric bypass situation, it might be worth asking about liquid forms of the same nutrients if you cannot handle a load of tablets.
      As for your situation with your twin, there is a research project going on into the DNA of Lyme disease, aiming to find out why some people with Borrelia infection develop chronic disease whereas others recover; they need twins for the research, one who is chronic and the other recovered. As you can imagine it is terribly difficult to find suitable pairs for this research so it could be hugely helpful to a lot of patients if you and your twin would participate: please have a look at the link for more info:


  15. Thanks for the simplified description of how methylation works. I see some remarks about ‘herbs’ having no usefulness in treating metabolic cycles such a methylation. Well, herbs are just concentrated foods. They come from leaves and roots usually. And they can indeed affect the metabolism, including some neurotransmitters mentioned in the chart above. Here is some proof: on LabCorp’s website, read the instructions for this test for catecholamines in the blood:!ut/p/c1/04_SB8K8xLLM9MSSzPy8xBz9CP0os_hACzO_QCM_IwMLXyM3AyNjMycDU2dXQwN3M6B8JG55AwMCuv088nNT9QtyI8oBPK_DWA!!/dl2/d1/L0lDU0NTQ1FvS1VRIS9JSFJBQUlnb0FNeUtibTZtL1lCSkp3NDU0a3N1eWx3ISEvN19VRTRTMUk5MzBPR1MyMElTM080TjJONjY4MC92aWV3VGVzdA!!/?testId=408120&criterion=Catecholamines%2C+Fractionated%2C+Plasma

    You will notice that the patient instructions say to avoid eating walnuts and bananas for a whole week prior to the test. (FWIW, bananas are herbs. Google it.) The reason? Obviously, eating them will skew the test results. The reason for this can be sorted out to a degree in the complicated chart at the top of this article. So a little homework – why would eating herbs affect a blood test for epinephrine, dopamine, and nor-epinephrine? (Hint: google bananas, amines, and MAO)

    Another interesting fact, some herbs have naturally occurring DAO (Broccoli sprouts for example). Extra points if you can find out how this can help a person with low MAO.


  16. Your article is very informative and helpful. However, I am still confused as to the best way to proceed. For instance, I understand supplementing with 5-MTHF can cause side effects, due to a lack other nutrients. Do you have any recommendations on finding a physician who understands all this and can provide some direction once you have your lab results. I know I have high homocysteine, but not sure what else or the best way to try to lower it.


    1. A friend of mine has recommended a therapist called Sean Bean. He works with various doctors. I have no experience of him myself but I am told he really knows his stuff.
      I think you will be able to find his website if you Google his name


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