Methyl-Free vs. Methylated: Do You Need a Non-Methylated Supplement?

Methyl-Free vs Methylated

You may have seen “methyl-free” on some of Seeking Health’s supplements

But what does this mean? And how do you know if you need a methyl-free product?

B vitamins are important for hundreds of processes in your body and many people take B vitamin supplements to feel healthy. Yet some sensitive individuals who take B vitamins experience nervousness and rapid heartbeat for minutes or days afterward. In certain people, these reactions have been attributed to a specific class of B vitamins called methylated B vitamins.

Methylated versus non-methylated is a novel concept that has become more popular since the release of “active” forms B vitamins in dietary supplements. Active forms of B12 and folate tend to include methylcobalamin and methylfolate, respectively. They are quite useful for those needing additional methylation support for a sluggish folate pathway, MTHFR gene variations, high homocysteine, and other methylation issues. 

Have you had reactions after taking methylated nutrients? If so, you might be wondering what to do.

Let’s back up to answer this question and first look at what methylation is and why it’s essential. Then we’ll discuss how to know if you’re methyl-sensitive and what to do if you are.

View Seeking Health’s Methyl-Free Products here.

What is a ‘Methylated’ Nutrient?

A methylated nutrient is a compound attached to a molecule made up of one carbon and three hydrogens, known as a “methyl group” (CH3).

Methyl Group - CH3

Common methylated nutrients include:

  • S-adenosylmethionine (SAMe)
  • L-5-methyltetrahydrofolate, or L-5-MTHF (an “active” form of folate, also known as just L-methylfolate)
  • Methylcobalamin (an “active” form of vitamin B12)
  • Trimethylglycine (TMG or Betaine)
  • Inositol
  • Choline
  • Phosphatidylcholine

You can see the word “methyl” within the name of some of these nutrients. In these cases, methylated nutrients are easy to identify. But in other cases, like choline or inositol, you may not realize they are methylated! 

What is a Methyl Donor?

Methylated nutrients are your body’s “methyl donors,” or nutrients that carry and transfer methyl groups from one compound to another. This process is called methylation, and it’s vital for the proper functioning of your body and overall health. (1)

Methylation-Simple

The body’s primary methyl donor is S-adenosylmethionine (SAMe), and it is created from methylated forms of vitamin B12 and folate, known as methylcobalamin and methylfolate. From B12, folate, and a compound called homocysteine, the amino acid methionine is formed. Methionine is a precursor to SAMe. Once SAMe is created, it can donate its methyl groups to various tissues and molecules throughout your body. This process is known as your methylation pathway. It is important to note here, that although there are many enzymes and nutrients involved in your methylation pathway, it is methylated B12 (methylcobalamin) and methylated folate (methylfolate) that initiate the methylation pathway and provide necessary methyl groups. If these nutrients are low, your methylation pathway could be sluggish.

Methylation-Simplified-Pathway

Why Does Methylation Matter?

Though the word “methylation” may be entirely new for you, it is a fundamental process for optimizing your health.

Methylation, and the opposite process of demethylation, is a cycle continually happening to keep your body’s “switches” turned on or off as needed, and all of the machinery running smoothly.  

You might be familiar with DNA methylation, which is the transfer of a methyl group onto your DNA, to literally turn a gene ‘on’ or ‘off.’ This concept is known as epigenetics. (1, 2, 3)

DNA-Methylation

Methylation allows for your organ systems’ functioning, such as the cardiovascular system, detoxification, and reproductive system. You need methylation to be working correctly to produce melatonin so you can sleep, balance important hormones, and assist with neurotransmitters that help maintain focus and a positive mood! (1, 2, 3)

In fact, our bodies use methyl groups to turn genes ‘on’ and ‘off’ in the various types of body tissues. Have you ever wondered how DNA is the same in every cell, yet we do not have eyeball cells in our belly button or ear cells on our lips? That’s because methyl groups sit on portions of our genes and tell them when to be read and when not to be read. This process of changing gene function without actually changing the genes is called epigenetics, and methylation plays a significant role in it. (1, 2, 3)

In short, methylation is an essential process that helps your body to develop and respond to its environment. It helps us move, transform, and grow! 

What Causes Poor Methylation?

Ok, so now you understand that methylated nutrients act as methyl donors by providing the methyl groups necessary to make methylation happen. But where do methyl groups come from in the first place? One of the primary sources is from folates in foods. The Latin root of folate is folium, as in foliage, since dark green leafy vegetables are rich sources of folate. 

Our body converts folate from foods into a special form of folate with a methyl group on it. This methylated ‘active’ folate is referred to as 5-Methyltetrahydrofolate (5-MTHF). In supplements, you may see this form of folate referred to as L-5-MTHF.

An important enzyme called MTHFR is needed to carry out the critical final step of making 5-MTHF. Unfortunately, up to 60% of the general population has slowed enzyme activity due to genetic variations within the MTHFR gene. In order for the MTHFR gene to function, it needs riboflavin (B2) as a cofactor and folate as a substrate. (4, 5, 6)

Folate-Pathway-Simplified

Many people have variations or single nucleotide polymorphisms (SNPs) in their MTHFR gene. This can produce a slower or inadequate MTHFR enzyme, contributing to lower methylfolate levels, and therefore poor production of SAMe for methylation.

Besides your MTHFR gene, other factors can slow down your methylation pathway. SNPs in your BHMT, CBS, and MTR genes can contribute to higher homocysteine levels, which can put stress on your methylation cycle. A build-up of homocysteine can also put stress on your cardiovascular system and lead to potential heart issues. (7)

There are many other factors involved, and it is best to work with a qualified healthcare professional to determine your methylation status. Your health professional will be able to order lab tests and evaluate your symptoms to see patterns that represent a dysfunctioning methylation pathway.

Testing and Treatment for Methylation Issues

Ask your healthcare professional to run the following tests to determine methylation function and status:

  • Methylation Panel blood test
  • Homocysteine blood test
  • B12 and folate marker test
  • Genetic test that evaluates MTHFR SNPs, as well as other methylation pathway genes such as MTR, MTRR, BHMT, and CBS

Learn 7 signs you need methylation support here.

If you or your health professional have concerns about methylation, most likely you will be prescribed a methylation support supplement that includes the following:

  • Methylfolate
  • Methylcobalamin
  • Choline
  • Trimethylglycine (TMG)
  • SAMe
  • And other B vitamins

These nutrients will act as methyl donors that help to push your methylation pathway, replenish folate and B12, and reach optimal health.

Methylated nutrients can be found in multivitamins, prenatal vitamins, B complexes, or standalone methylation support products. 

Side Effects of Methylated Nutrients 

Some people react poorly to methylated nutrients. If you have had adverse side effects after taking anything with B vitamins in it, you may be sensitive to methylated nutrients.

You might experience: 

  • Nervousness
  • Rapid heartbeat
  • Headaches
  • And possibly other uncomfortable symptoms

These may take days to subside and can cause extreme discomfort in some. Keep in mind that the side effects mimic many other common concerns and issues, such as intolerances. This is why methylation side effects must be addressed with a qualified healthcare professional to rule out any other possibilities or sensitivities. 

However, if you have determined that your symptoms are solely associated with methylated nutrients, then you may be a perfect candidate for a “methyl-free” alternative.

Methyl-Free Nutrients 

Methyl-free supplements are formulated to be free from methylated nutrients and instead contain methyl-free alternatives.

Though there are not methyl-free alternatives to every methylated nutrient, there are alternatives to B12 and folate.

You can find these alternatives in some multivitamins, B vitamins, or prenatals that are labeled:

  • “Methyl-free” 
  • “Free from methyls”
  • “Non-methylated”
  • “MF”

You can also find them as standalone B12 and folate products.

See all of Seeking Health’s Methyl-Free Products here.

Remember that methylated folate and B12 are what helps to provide the methyl groups to create SAMe (your body’s main methyl donor). However, your body can create methylfolate and methylcobalamin from bioactive, non-methyl forms.

When you supplement with non-methylated forms, you are still able to provide your body with folate and B12. It just takes a few more enzyme steps before the methyl groups are available. This slower delivery may be beneficial to people who are sensitive to methylated nutrients.

Non-methylated folate and B12 can be found in dietary supplements as the following names:

  • Methyl-free folate is available as folinic acid (also known as calcium folinate on your supplement label)
    • Folinic acid is only a couple of enzymatic steps behind the most bioavailable form of methylfolate, 5-methyltetrahydrofolate (5-MTHF). It is therefore easy for your body to convert folinic acid into the active form 5-MTHF. (Note that folinic acid is NOT to be confused with the human-made version of folate, folic acid, which you will never find in any of our products!)
  • Methyl-Free B12 is available in two forms,  Hydroxocobalamin and Adenosylcobalamin
    • Both of these become converted into methylcobalamin in the body,  by providing the necessary ‘cobalamin’ groups needed to create methylcobalamin. 

Non-Methylated Nutrients & Methylation

So here is an important question: If you take these non-methylated versions, do they still support methylation and MTHFR gene mutations?

The answer is yes! In fact, methyl-free versions are great bioactive alternatives to methylated nutrients. This is because they rely on your body to turn them into the “active” forms, which is thought to be self-regulating.

Let’s look at the Folate Pathway as an example:

Folate-Pathway-Simplified

As you can see, folinic acid (non-methylated version of folate) is only two steps behind L-5-methyltetrahydrofolate (5-MTHF), the methylated, active version of folate that you need. 

In fact, you will see that food folate (such as folate from dark leafy greens) can be upwards to 8 steps behind 5-MTHF. That means if you avoid folate supplementation altogether due to side effects, and try to get folate solely from food folates (i.e. leafy greens), your body has to do a lot more work to create the active form of folate, methylfolate (5-MTHF). 

When it comes to supporting your methylation cycle (including the MTHFR gene), these non-methylated forms are more enzymatically efficient than food forms of folate.

There are things you can do to even further improve the folinic acid conversion to methylfolate.

Look at the Folate Pathway again. Check out the MTHFR and SHMT genes, both which help to convert folinic acid to 5-MTHF.  You can support them by ensuring adequate nutrient cofactors, while reducing the inhibitors (stress, medications, etc). MTHFR requires riboflavin as a cofactor, and SHMT requires magnesium as a cofactor. Getting adequate riboflavin and magnesium in your diet will help this conversion along.

MTHFR-cofactors-inhibitors

Folic acid is commonly prescribed by doctors today as a “folate” supplement, however, it has the ability to slow several enzymes in the Folate Pathway, ironically reducing folate levels overall. It can even block folate receptors in some cases.*

Stress, toxins, and certain medications can further reduce MTHFR enzyme function. Speak with a qualified healthcare professional about detoxification marker testing (such as organic acids testing) to determine if your toxic overload may be preventing proper methylation. Taking these actions to improve your folate pathway, and consuming folinic acid, helps to replenish your levels of methylfolate precursors, which, in turn, helps produce methylfolate naturally.

Non-Methylated Nutrients & MTHFR

By now, you understand that your body has the ability to produce methylfolate from precursors. A slowed-down MTHFR gene variation doesn’t mean that you need to supplement with methylated nutrients. Instead, you can ensure adequate nutrient cofactors to support your MTHFR enzyme function (i.e. supplementing with the MTHFR enzyme’s primary cofactor, riboflavin). Work towards eliminating stress, toxins, and folic acid. Talk to your healthcare provider about supplementing with methyl-free folate (folinic acid) and methyl-free B12 (hydroxocobalamin or adenosylcobalamin).

Methyl-Free Supplements

Seeking Health offers methyl-free options for prenatal vitamins, multivitamins, and B vitamins. Each of these products contain bioactive folinic acid, hydroxocobalamin, and adenosylcobalamin as methyl-free forms of folate and B12.

  • Optimal Prenatal Methyl-Free: A powerful, nutrient-dense prenatal vitamin that is free from choline and inositol. It features folate as folinic acid, and B12 as hydroxocobalamin and adenosylcobalamin.
  • Prenatal Essentials Methyl-Free: A concise, yet powerful prenatal vitamin that is free from choline and inositol. It features folate as folinic acid, and B12 as hydroxocobalamin and adenosylcobalamin.
  • Hydroxo B12 with Folinic Acid: This delicious and optimally-absorbing lozenge contains potent servings of methyl-free B12 (hydroxocobalamin) and folate (folinic acid).*
  • Hydroxo B12: Potent serving of hydroxocobalamin in a delicious lozenge format.
  • Adeno B12: Potent serving of adenosylcobalamin in a delicious lozenge format.

Formulated by methylation and MTHFR expert Dr. Ben Lynch, Seeking Health methyl-free formulas were designed to support your methylation pathway without the uncomfortable side effects!*

B12- & Folate-Free Supplements

Are you looking for products that are completely free from B12 and folate? You’ve come to the right place! Seeking Health has options for you:

  • Optimal Start: A multivitamin that is completely free from folate, vitamin B12, D3, K2, iron, and copper to accommodate those with sensitivities, and allow for customized dosing of these nutrients
  • B-Minus: This B complex is free from B12 and folate to allow for customized dosing of these nutrients.

Keep in mind that B12 and folate are essential vitamins for methylation and, therefore, fertility, heart health, sleep, mood, and so much more. Many customers love to pair these B12- and folate-free options with our popular Active B12 with L-5-MTHF or Hydroxo B12 with Folinic Acid for independent and customized dosing of these critical nutrients.

The Bottom Line

Methylation is a necessary process in your body that involves the transfer of a “methyl group” from one substance to another. You get these methyl groups from methylated nutrients, such as methylfolate. Methylation keeps all of your “machinery” working right, including major organ systems, and even genetic expression.

However, many sensitive individuals get side effects such as nervousness and rapid heartbeat after taking methylated nutrients. Though methylfolate is essential for methylation, it is not the only option for supporting methylation and your MTHFR gene. Folinic acid (a non-methylated form of folate) and hydroxocobalamin or adenosylcobalamin B12 (non-methylated forms of vitamin B12) are excellent, bioactive alternatives that can support your methylation pathway. For individuals who are sensitive to methyl groups, these methyl-free alternatives might just be the best route. 

Check out Seeking Health’s line of methyl-free prenatal vitamins, multivitamins, and B complexes to help support optimal health without the uncomfortable side effects!*  

View Seeking Health’s Methyl-Free Supplements here.

References

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734882/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147084/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174260/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430358/
  5. https://pubmed.ncbi.nlm.nih.gov/23437053/
  6. https://pubmed.ncbi.nlm.nih.gov/26939404/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326479/

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

† This information is for educational purposes only. No product results are implied.

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Comments (3)

  • Avatar

    Marilyn

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    Hidy Ben, Myself and two adult children all work with having MTHFR. Therefore, I like to print many of your articles that come via your newsletter. It would be really really wonderful if you were able to ask your ‘tech’ people to have a print version of each article to save me printing lots of extraneous things that appear on the page where the interesting article is (you know, saves paper, time, ink, etc.!) Lots of thanks in anticipation, Marilyn

    Reply

    • Avatar

      Karen Ward

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      Thank you for your comments, we will work on a better printed version of the articles.

      Reply

  • Avatar

    Barbara Krall

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    THANK YOU, DR LYNCH for this comprehensive yet very understandable article! I have been a fan of Seeking Health products and your website for several years. Methylation and MTHRF can be complicated subjects to understand — I have read extensively about it, think I understand it but have never been able to explain it simply to someone else.

    Luckily, I have one of the mildest varieties of MTHFR (hetero C677T). Although, when initially starting folate supplementation, even my functional medicine PCP way overdid it with 2 mg of (6S)-5-Methyltetrahydrofolic acid glucosamine salt. After my body ramped up its methylation cycle and then ran out of potassium to feed the increased rate of cell division, I eventually had “panic attacks” (really low potassium attacks).

    I am one that does much better with the non-methylated folinic acid / calcium folate.

    Reply

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