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Methylation Advice Please


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Every time I try to discuss methylation with my DD's LLMD, he tells me not to worry about it b/c treating her lyme is the big focus. My gut tells me that I need to consider and address her methylation results, especially as we continue to detox during her lyme treatment. My DD is constantly in an emotionally restless state (we never know when we're going to have a good or bad day). Her tics, rages, and ability to be and feel " calm and present" wax and wane with her medical treatment. Here are my concerns re: her 23 and me results:



CPOX4- GT (1/2)

CYP1A1- CT (1/2)

CYPD2D6- AG (1/2)

GSTP1- AA (2/2)

NAT2- AG (1/2)



COMT V158M & H62H +/+

DAOA- AA (2/2)

GAD1- AA (2/2)

MAO-A +/-


Folate One-Carbon Metabolism/Methylation:

CBS C699T +/+

CBS A360A -/-

MTHFR C677T +/-

BHMT-02 & 08 +/-





I've done nutrahacker and tried to read (with many failed attempts) the Heartfixer document. I'm most concerned with her homozygous CBS, COMT, DAOA, and GAD1 (high glutamate/low gaba) mutations. I also can't figure out if she is an over/under methylator. I don't know what to make out of her detoxification mutations. When I showed the doctor her 23 and me results, he said to "watch out" for histamine???


I'd love any advice you have to point me in the right direction for how to interpret her results, recommended supplements and a treatment protocol.

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I am no expert on methylation or the various mutations; hopefully, someone far more studied (LLM, for instance) will be able to give you some guidance there.


In the meantime, with respect to histamine and whether or not your child is an under-methylator or an over-methylator, have you seen this document?




This matrix by Dr. Carl Pfeiffer was very helpful to us in terms of clinically assessing our DS.


Best to you!

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COMT+/+ indicates over-methylation

CBS+/+ may effect ability to process ammonia and taurine


My source: Dr. Amy Yasko book available free as .pdf online here (you can do a word search. It doesn't cover all of the SNPs you listed in your post, but it does cover COMT, CBS, MAO, MTHFR, BHMT, and VDR):




It provides description of what the SNPs are, what they effect, and ways you and your doctor can discuss to address them.

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With both COMT + and MTHFR +, I don't think it's a question of over or under methylation. It's both. Ben Lynch describes it as driving with one foot on the gas and one foot on the brake.


My DD is in a similar situation - both in terms of her snps and lyme/bartonella. Every body is different, but here's what we've found helpful:


CBS - my DD is only CBS +/-, so not as bad a predicament as you face, but we need to avoid the supplements commonly used for Lyme detox. No NAC, no alpha lipoic acid, no tumeric, no glutathione, no epsom salt baths. However, I don't restrict the foods you're supposed to avoid with CBS. My DD is recovering from Pans induced anorexia - the last thing I'm going to do is give her a list of foods to avoid. Instead, we just focus on reducing ammonia and managing sulfates/sulfites. She takes:

  • 150 mg/day molybdenum
  • 500 mg carnitine (important for her b/c she doesn't like beef, pork or chicken, so she doesn't get enough of this in her diet)
  • 500mg arginine + 250 mg ornithine 3x/day - this not only fuels the urea/krebs cycle and helps the body eliminate ammonia and some toxins thru the kidneys, it also reduces inflammation in the endothelial layer of the blood vessels. This is really helpful for bartonella and for DD, it makes a huge difference in her stamina/fatigue
  • sometimes we've also used yucca root or habiscus sabdarifa for ammonia but since adding the arginine, not so much, as the arginine gives us both ammonia reduction and inflammation reduction.


  • a B complex that doesn't contain B9 (folate) or B12. We use Seeking Health's B Minus, but I cut the dose into 1/4. A full capsule is far too high a dose IMO and my DH and DD don't feel well on it. I buy empty size 0 gel capsules from amazon and divide one capsule into 4 capsules.
  • methylfolate - you need to experiment with dose. My DD12 only needs 135 mcg (only used 67 mcg when she was younger) and my DH takes 400 mcg from Solgar (Metafolin). I recommend Yasko's Methylmate B liquid methylfolate to start with. Each drop is 67mcg, so you can experiment with changing doses in small increments until you zero in on what works best. This is easier with a liquid than with tablets, so I'd start with the Methylmate B.
  • B12 - because you have COMT, you probably don't want to use methylB12. I like Seeking Health's adenoB12 or hydroxyB12. Supposedly, you only absorb 10% of a sublingual B12, so 3000mcg nets you 300 mcg into the blood stream. You need to try both types to see which your DD prefers. There's no way to tell without experimenting.

For COMT -

  • despite needing methylfolate for MTHFR, your DD is staying ramped up on adrenaline a lot of the time. So Lynch suggests adding niacinamide (flush free niacin). My DD takes 100mg daily (or you can split the pill (Source Naturals makes a 100mg tablet) and give 50mg twice a day to even things out)
  • the additional niacinamide helps with anger - a lot! It's also a good antidote for when you're tweaking methylfolate dosing and give too much. 50-100mg niacinamide will calm things down w/in 30 min.

For MAO -

  • if addressing MTHFR and COMT aren't enough to even out the moods, copper (1-2mg) can help MAO spin a little faster. You also need to avoid OTC cold and cough meds that say "do not take if you're using an MAO-I" - having an MAO+ already inhibits MAO, so you don't want to take anything that will make it work slower still

Lyme detox - you get clobbered with messages that tell you you need to detox with Lyme treatments. This is hard when you're CBS+. So instead, I follow Stephen Buhner's advice, which is to focus on inflammation. If you keep inflammation down, the body is better able to detox itself. In addition to the arginine, I use 1/2 tsp of Japanese Knotweed and 1/2 tsp Red Sage - both 3x/day and on days where herxing is a concern (as we're currently pulsing tindamax), I do the Japanese Knotweed 6x/day. Again, I use the empty gel capsules - one size 00 capsule holds a little more than 1/4 tsp of liquid. You have about 1 min before the capsule will start to dissolve, which is enough time for DD to swallow the capsule. No way would she drink some of the herbs unless the taste is masked by the capsule.


I know I didn't address the other snps. It's been a few years since this was my main focus, so I don't have much input on the others. Addressing MTHFR, CBS and COMT were enough to get DD stable emotionally, (when not in a flare). We've also had to treat the chronic infections but addressing the methylation issues definitely helped a lot. In doing this, DDs allergies became almost non-existent. One or two days in the spring, she'll need a quercetin, but most days, they don't bother her anymore.


hope this helps give you a few ideas

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Thank you for your replies! I have read some of Dr. Phieffer and Yasko's works, but I will go back and dive deeper into them.


LLM- I really appreciate your detailed reply. I'm going to research all of your suggestions and see what we can include in her daily protocol. My daughter has had restrictive eating problems and constipation since birth. She is very low on the weight/growth chart and some years wasn't even on the chart. The only thing that helped her to gain weight was BRAVO yogurt. Within the first two months, she gained 6 lbs and continued to put on another 14 lbs the following nine months. Somehow the colostrum and GCMAF within BRAVO helped tame the inflammation and regulate her bowel movements. We also went gluten free and are low dairy with her. So, she eats a ton of eggs and meat. I won't remove these from her diet, so tackling her CBS mutation with supplements is the only way for us to go.


Also, your point about detox vs. inflammation is so well said. I have been hesitant to continue with our epsom salt baths for detox knowing she is CBS +/+. We are currently treating her lyme with just Beyond Balance herbs (and a few other vitamins like zinc, lithium orotate, fish oil, and gaba/l-theanine for anxiety). We may go back to antibiotics once school gets out. While I'd like to move over to Buhner, my LLMD tells me it's too much work plus the BB herbs have a palatable taste. The only problem with BB is you don't know what is working and what isn't with an herb combo. Maybe I'll just experiment with some of the Buhner herbs on the side...


I also wonder if activated charcoal can help with the CBS mutation or something like it help bind to the toxins and soak them up?

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