6 Helpful Steps to Treat MTHFR

I just found out I have an MTHFR variant(s). What should I do first?

1. Try to remove all sources of folic acid from your diet

You should be particularly concerned about folic acid from dietary supplements, vitamins, prescriptions and/or fortified foods. Synthetic folic acid is not just ineffective for people with MTHFR variants; it’s actually counterproductive. And some studies have even pointed to it as a suspect regarding cancer.

2. Prepare the body's Methylation Biopathway

  • According to Dr. Neil Rawlins, NAC is one of the best nutrients to begin with if you have MTHFR.  NAC helps replenish glutathione in the body which is especially helpful for protecting organs and detoxifying things like heavy metals, BPAs, phthalates, etc.  Consider starting on a dose of 600-4,000 mg a day (1,200-3,000 mg being a solid range for most - based on tolerance). Take the NAC for 1-2 weeks before beginning with the active hero nutrient discussed below in step 3.  Methylfolate will promote & utilize the intracellular glutathione, so you'll want to be sure you've got that onboard and have already "primed that pump", so to speak.  NAC is an affordable option for increasing intracellular glutathione levels.  Those dealing with bipolar disorder, peaks and troughs (or other challenges where neurotransmitters build up or deplete quickly) can often benefit from a monoamine reset.  NAC can help with this at the higher dosage levels, ~4,000 mg a day. 

  • Consider taking a clean multivitamin that has no folic acid and no B12 especially cyanocobalamin (this is a VERY poor, synthetic form of B12 that is not absorbed well and contains cyanide - stay away from it). Learn more about active B12 forms. A multivitamin without folate or B12 can be VERY hard to find, but it will help you prime the methylation pathway before you introduce the active ingredients specifically designed to support the MTHFR variants.

Be aware of Vitamin B6 as Pyridoxal-5-Phosphate (or P-5-P). 
Some will do well with higher doses of this vitamin (i.e. >6 mg), but others absolutely will not. Another genetic mutation can cause P-5-P buildup or toxicity in the body which can be identified by tight-band headaches that go away when you stop taking the P-5-P (B6). Consider taking a multivitamin that has a lower dose of P-5-P (B6) to start, unless you know you tolerate this vitamin form well.

Make sure you have some important co-factors onboard

  • Magnesium is an important co-factor that most are deficient in, so getting a healthy dose (400-600 mg daily) of a highly bioavailable form is extremely beneficial (consider a liposomal-like delivery). This mineral is leveraged by the body in over 300 enzymatic conversions. Possible bonus benefits: it may bring more calm, help normalize some stress responses, provide better balance to sleep issues, and may even lower hypertension.
  • TMG (Trimethylglycine or Betaine) may be helpful for some. It reduces homocysteine, so if you have high homocysteine (as tested properly by a doctor), you may benefit from taking higher doses of TMG – consider a dosage of 600-1,800 a day depending upon your homocysteine levels. NOTE: Not everyone with an MTHFR variant has high homocysteine. 
  • DMG (Dimethylglycine) is similar to TMG in that it reduces homocysteine, however, some might find it more helpful than TMG. Both TMG and DMG reduce homocysteine levels by sending methyl groups into the methyl pool (this produces SAM-e (S-Adenosyl methionine) from the homocysteine)
  • Active B12 – there are 3 types to choose from, but hydroxocobalamin is the most well-tolerated active form and the one we recommend; HOWEVER...

...if you know your specific genetic results for Single Polymorphism Nucleotides (SNPs) – COMT 158 and VDR Taq, check out the chart on our page about choosing the best active B12 form and discovering which one is right for you.

If you don’t know the specific results of those genetic SNPs, check out our brief videos below. You can always talk to your healthcare professional, but just know that it’s sometimes difficult to find someone with specific knowledge about Active B12, the differences between the various forms, and why some would be better than others for certain folks to take.

3. It’s third on the list, but it’s THE REALLY BIG ONE, L-METHYLFOLATE

Add a quality L-Methylfolate supplement to your nutrition routine. Start with a lower dose (400-2,500 mcg) and slowly increase if you have symptoms or conditions which suggest you might do better with a higher dose. Take some time to review our dosage video if you have concerns about how much L-Methylfolate to take.

Also, check out our Methylation Protocol page which provides 4 different free protocol downloads targeting 4 specific MTHFR symptom sets. Each protocol guide gives step by step details for nutrients, dosage increments and product options. 

If you’re considering L-Methylfolate to target a specific condition, there are some prescription products which were developed with just that in mind, though it’s important to realize they contain dyes, allergens and extra fillers. See a comparison chart below. Pay particular attention to the dosages of active ingredients to give you an idea of what you might want to target.

Medical Food Product



Other Actives

Inactive Ingredients

Rx Only

Cerefolin® NAC


Alzheimer’s prescription targeting brain health


5,600 mcg 

Methylcobalamin 2 mg



600 mg

Microcrystalline Cellulose, Opadry II Blue 07F90856 (Hypromellose, Talc, Titanium Dioxide, Polyethylene Glycol, FD&C Blue #2-Aluminum Lake, Saccharin Sodium), and Magnesium Stearate (Vegetable Source)


Deplin® 7.5 

Adjunct Depression prescription targeting increased serotonin production

L-methylfolate Calcium 

7,500 mcg 



Dibasic Calcium Phosphate Dihydrate, Silicified Microcrystalline Cellulose 90, Silicified Microcrystalline Cellulose HD 90, Opadry II Blue 85F90748 (Polyvinyl Alcohol, Titanium Dioxide [color], PEG 3350, Talc and FD&C Blue #2[color]),L-methylfolate Calcium, Magnesium Stearate (Vegetable Source), and Carnauba Wax


Deplin® 15

Adjunct Depression prescription targeting increased serotonin production


15,000 mcg 



Dibasic Calcium Phosphate Dihydrate, Silicified Microcrystalline Cellulose 90, Opadry II Orange 85F43102, (Polyvinyl Alcohol, Titanium Dioxide [color], PEG 3350, Talc, FD&C Yellow #6[color], FD&C Yellow #5[color], FD&C Red #40[color] and FD&C Blue #2[color]), L-methylfolate Calcium, Magnesium Stearate (Vegetable Source), and Carnauba Wax.



Diabetic prescription aimed at neuropathy


3,000 mcg

Methylcobalamin 2 mg


35 mg

Dibasic Calcium  Phosphate Dihydrate, Microcrystalline Cellulose 90, Microcrystalline Cellulose HD 90,  Pyridoxal-5´-Phosphate, Opadry II Purple 40L10045 (Polydextrose, Titanium Dioxide, Hypromellose 3cP, Hypromellose 6cP, Glycerol Triacetate, Hypromellose 50cP, FD&C Blue #2, FD&C Red #40, Polyglycol 800), Microcrystalline Cellulose 50, Opadry II Clear Y-19-7483 (Hypromellose 6cP, Maltodextrin, Hypromellose 3cP, Polyglycol 400, Hypromellose 50cP), Lmethylfolate Calcium, Magnesium Stearate, Methylcobalamin, and Carnauba Wax.


NeevoDHA® – Prenatal 

Prescription aimed at healthy pregnancy


1,130 mcg

Methylcobalamin1 mg


25 mg

Gelatin (Bovine), Glycerin Blend (glycerin, sorbitol), Titanium Dioxide (color), FD&C Blue #1, Ethyl Vanillin, FD&C Red #40 Contains Soy.


What should I order?

If you’ve never taken any products for MTHFR before and are not sure what to order, we’d suggest our MTHFR Beginner's Bundle which contains four products [Sucrosomial Magnesium, Non-Methylated Multivitamin, Hydroxocobalamin & Methylfolate 2.5]. Also, we’d suggest reviewing our Methylation Protocol options as well as watching our dosage video.

If you’re targeting a particular symptom or condition, consider a dosage level appropriate to that specific need. It’s worth noting that L-Methylfolate crosses the blood-brain barrier.

How much methylfolate should I take?

As always, talk to your healthcare professional. And check out our Methylation Protocol and dosage pages so you can have a sense for how much might be right for you to try.

What side effects might I encounter?

Remember, these are vitamins, so the number and type of side effects experienced are going to typically be much lower than it would be for a pharmaceutical drug. But be smart. If you’re very sensitive to drugs, vitamins and supplements, do your research and start low and go slow to increase. Make only one change at a time – whether you increase your dose of the same nutrient or add another nutrient into your routine.

Some side effects you could encounter if you take too much methylfolate for your body which is often referred to as ‘over-methylation’:  

  • flu-like symptoms (body aches, rash, headache, fatigue)
  • irritability
  • anxiety
  • inability to sleep
  • mood shifts
  • heart racing/palpitations

For most, it’s going to be up to the individual to determine how much and what kind of dosage experimenting you want to try or not.

Know that any reaction you have will likely be temporary, as these B vitamins do not stick around in your system – what your body doesn’t use will be peed out over time. 

Moreover, if you have an ‘over-methylation’ experience Dr. Neil Rawlins suggests taking NAC and/or Glutathione to help reduce methylation reactions and some of those unwanted 'over-methylating' symptoms (these are also both excellent nutrients to take along with your methylfolate in order to promote even greater detoxification and can be thought of as excellent supporting cofactors for methylfolate).  Dr. Ben Lynch recommends taking 50 mg of nicotinic acid every 30-60 minutes to counteract over-methylation symptoms. If you have symptoms of anxiety or irritability and you’re pretty sure it’s due to excessive methylfolate or neurotransmission, try the Niacin (not the Nicatinomide form). Dr. Lynch has found that people who have this kind of experience can stop the reaction in a very short amount of time using the nicotinic acid. 

4. Seriously consider changing your lifestyle and making it more “CLEAN.”

Try to adopt as many of these healthy eating habits as you can - even doing one of them is beneficial, so don’t think of this as an “all or nothing” list:

  • Increase purified water intake (without chlorine/chloramine or fluoride) - consider an NSF-certified drinking water filter you can attach to the tap you choose to drink from (use discount code 434333 at checkout to get a 5% discount on your order) as well as an additional filtration system that also alkalinizes the water according to your preferred settings. Jamie Hope uses these systems together daily and so Methyl-Life® has partnered with them on your behalf. The latter is a bit more of an investment, but when you think of your health and the fact that your body is 55%+ water, you want to make sure the source you're getting regularly is ultra-clean and encouraging health
  • Cut out antibiotic and hormone fed foods
  • Consider a gluten and dairy free diet - as hard as this one is, it makes a big difference (dairy actually contains a folate binding protein which we believe competes for folate receptors)
  • Get as much nutrition from whole foods as possible
  • Eat smaller meals more often
  • Remove inflammatory foods (consider an IGG or IGA food allergy test to reveal the ones that are specifically problematic for you personally)

5. Consider taking other key nutrients that benefit those with MTHFR - IF you tolerate them well.

And as with all nutrients, please LISTEN TO YOUR BODY and do what’s best for you – not everyone tolerates all ‘beneficial’ nutrients:

N-acetylcysteine (NAC)

Vitamin E



Vitamin C


Silymarin (Milk Thistle)


Vitamin D3





6. Reducing toxic burden

Lower your exposure to toxins and work to rid your body of them by taking some of these steps

The easiest places to start:

  • Sweat regularly (get in the sauna or exercise)
  • Don’t eat, drink or especially store in plastic containers that have BPAs or phthalates
  • Watch out for BPAs in unexpected places (most receipts are printed on paper with BPA)
  • Avoid using nitrous oxide increasing drugs (i.e. laughing gas at the dentist)
  • Drink “clean water”
  • Use the recirculating fan in the car when behind other vehicles in traffic (especially the big dirty ones spewing fumes – like semi-trucks, buses, garbage trucks, etc.)

Above and beyond:

  • Consider a whole-house air purifier/cleaner
  • Have mercury metal fillings removed by a qualified dentist
  • Consider replacing carpet with tile or wood (low VOCs)
  • Install a whole house water filter (remove chlorine/chloramine)

Receiving a diagnosis that requires lifestyle changes can be incredibly overwhelming. Remember, this is not an “all or nothing” set of rules to follow. Start where you can, and as your body responds, you will learn more, then as you slowly get used to the ideas, gradually take more steps. 

Remember, this whole process is like running a marathon, not a sprint.

Be encouraged - your healthiest life is within reach!



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