Methylated Multivitamin vs Regular Ones: Which is Better?

These days, it's difficult to go more than a few hours without seeing an advertisement for some kind of vitamin or supplement, at least in markets like the United States, where regulations on advertising them are lax. To stand out, many of these supplements will make bold claims, accompanied by footnotes that explain that there's no backing from the FDA and that they haven't been evaluated for those claims, as a way to waive any liability and put the burden on the consumer.

In other words, it's very difficult to tell what's legitimate, what's nothing more than buzzwords, and what may have some benefit with tempered expectations. Even with advanced degrees in medicine and years of experience, it can be tricky to comb through it all. That's why I do what I do, both here on this blog and on my YouTube channel; I want to help clear up misconceptions and dig into the truth beneath it all.

One area that's worth looking into is the trend of methylated vitamins. Methylated vitamins can come as individual vitamins or, more commonly, as methylated B-complex multivitamins. What does it mean for a vitamin to be methylated, is it beneficial to your health, and what should you keep in mind if you're considering taking them? Let's talk about it.

What are Methylated Vitamins?

First, let's start at the beginning. What are methylated vitamins, and how do they differ from normal vitamins?

In chemistry – don't worry, I'm not going too deep into it – a molecule made up of three hydrogen atoms and one carbon atom (CH3) is called a methyl group. It's a very stable molecule as part of a lot of different organic compounds and is found throughout the body and in nature nearly everywhere.

When you consume vitamins, they are not methylated by default. For example, folate is Vitamin B9 and has a rather complex chemical structure, but there are no methyl groups attached to it normally. The problem is that your body doesn't use folate or folic acid on its own.

In order for your body to use vitamin B9, it needs to be methylated first. In your body, an enzymatic reaction strips certain hydrogen atoms from the vitamin and adds methyl groups in their place. These methylated derivatives of B9 can then fuel different biological processes.

A methylated vitamin, then, is a supplemental vitamin source that provides pre-methylated versions of these vitamins.

Why are Methylated Vitamins Potentially Valuable?

Taking a look at what I wrote above, a simple logical train of thought might be:

• Your body needs these B vitamins to remain healthy.
• Your body can't use B vitamins normally; it needs to process them first into a usable form, methylated vitamins.
• Why not provide the vitamins in a methylated form so you get more of the good stuff faster and more easily used?

It's a reasonable and logical train of thought, but it doesn't account for several important questions. I'll get to those in a moment.

It's undeniable that our bodies need B vitamins to function properly. Those vitamins are used in countless enzymatic processes, reactions, and systems throughout the body. They can be responsible for proper gene expression, DNA repair, cognitive function, heart health, and much more. If nothing else, we can tell this simply by observing what happens if someone is deficient in a B vitamin.

If there are limitations on being able to use B vitamins in their normal form, maybe taking methylated versions of those vitamins could provide benefits.

So, what were those questions worth bringing up? Here are a few:

• Does your body need to regulate the amount of methylated vitamins available to it at any one time?
• Does the process of digestion destroy methylated versions of vitamins more readily than their non-methylated forms?
• Does your body absorb and store methylated vitamins through digestion as effectively as the normal versions?
• Are there adverse effects to consuming methylated versions of vitamins instead of normal vitamins?

These questions are not easily intuited, and they aren't easily answered.

Does the Science Show Any Benefits for Methylated Vitamins?

Now, we come to the crux of the issue. Methylated vitamins have been available for over a decade, which is plenty of time for studies to be performed and data to be gathered. Does any of the science back up any potential benefits of taking methylated vitamins?

Methylated Vitamins for Depression and Anxiety

Methylated vitamins are commonly studied for their potential effects on mental health. In particular, several studies have looked at the effects of methylated vitamins on depression and anxiety generally, on depression management specifically, and as a mono treatment for treatment-resistant depression.

One study looked at individuals with depression and asked them to add methylfolate to their current antidepressants. While this study showed a statistically significant improvement in reported conditions, there are two significant drawbacks to this study.

The first is that it's reliant on patient reports, which can be unreliable and subject to the placebo effect. The second, also related to the placebo effect, is that the study was not blinded or placebo-controlled. Sure, it showed an improvement, but there's no way to tell if that improvement is relevant compared to a placebo in a trial without performing that trial.

A second study was a case study of one individual. Her long-term treatment-resistant depression seemed to improve with the addition of methylated folate to her diet. A test found an enzyme alteration of MTHFR, which may be relevant; keep that in mind for later. Regardless, a single case study isn't necessarily reflective of how a supplement can affect the broader population.

The third study I'm looking at is a systematic review and meta-analysis of numerous data sources. These tend to provide a broader perspective and can draw from information that is harder to find, but it's worth keeping in mind that they reflect what studies exist, but they can't add authoritativeness to existing studies. They can qualify and evaluate the data they use, however.

This meta-analysis reflects the above; methylated vitamins like methylfolate may potentially help reduce depression symptoms. More studies are needed to know for sure how well they will work on the broader population, if there are extenuating factors like MTHFR mutations, or if there are disqualifying side effects in the broader population or over the long term. More on all of that later.

Methylated Vitamins for MTHFR Polymorphism

The human genome has many, many genes, and the expression of those genes determines an immense amount about us all as individuals. One particular gene and its mutation, known as MTHFR polymorphism, is fairly common. Effectively, it causes a lower level of the enzyme necessary to methylate folic acid, which results in folate deficiencies. Estimates place this mutation as affecting around 1% of African Americans, 10% of Caucasians and Asians, and 25% of Hispanics.

For people who have this mutation, the usual recommendation is taking a folate supplement. However, there may be some potential that taking methylated folate instead could be more beneficial. Some studies indicate that methylfolate bypasses this deficiency; others conflict. More study is needed.

Methylated Vitamins for Other Purposes

You might have noticed that most of what I've referenced above has looked at methylfolate, but methylfolate is only one of the B vitamins that can be methylated. This is because it is also, by far, the most commonly studied methylated vitamin. It's not the only one on the market, though.

Various claims are made about methylated B vitamins in a complex supplement containing several of them at once.

• They may help prevent birth defects related to folate deficiency, but insufficient studies have been done for the FDA to recommend it over standard folate.
• They may help reduce the effects of schizophrenia, though relatively few studies on relatively few people have been performed.
• They may help provide energy to bolster metabolic function. This claim largely comes from supplement manufacturers producing pre-workout supplements and seems to have little or no study performed.

Overall, relatively little data exists for these additional possibilities, and for now, the FDA doesn't recommend methylated vitamins in general.

Are There Risks to Taking Methylated Vitamins?

If methylated vitamins provide even small benefits, there's no harm in taking them, right? Unless there is some harm in taking them. Unfortunately, there may be some serious evidence to consider in the adverse effect profile of methylated vitamins.

Methylated Vitamins and Cancer

Cancer is, in simple terms, a mutation in the DNA of a cell that causes it to replicate without natural restrictions; it replicates itself with that mutation, growing out of control and causing problems. In order to replicate and grow, it needs fuel, and that fuel comes from (among many other places) vitamins and nutrients you consume.

There's some suspicion that methylated vitamins, which bypass the body's ability to regulate how much is in your system through enzymatic reactions, can accelerate cancer growth. They don't necessarily seem to increase the risk of cancer developing, but if it does develop, taking methylated vitamins might accelerate how quickly it progresses. This can also vary between different vitamins and different cancers, so it's impossible to adequately generalize, especially with the limited studies and information available.

Methylated Vitamins and Cardiovascular Disease

Cardiovascular disease is a leading cause of death around the world, so it's reasonable to examine any supplement for its effects on CVD, positive or negative.

In this case, there are conflicting studies; some seem to indicate methylated vitamins might help regulate DNA methylation and lower CVD risk; others worry that imbalancing natural processes through megadoses of methylated vitamins increase CVD risk. For now, further study is needed.

Should You Take Methylated Multivitamins?

Sooner or later, we all just want someone to tell us what to do with reliable and trustworthy information backing them. So, should you consider taking methylated multivitamins, or not?

The one most likely reason why you would want to take methylated multivitamins is if you are one of the people with the MTHFR gene mutation that reduces your vitamin uptake, and you need to get more into your system to avoid a deficiency. This is something you need to have tested by a doctor and you'll need to work with your healthcare team to determine the appropriate course of action.

As always, my recommendation is to talk to your doctor directly about your concerns and ask if methylated vitamins might help. I would not recommend taking supplements without medical guidance for two primary reasons.

The first reason, as you might expect from reading the above, is that there's relatively little data and few human studies that indicate tangible, trustworthy benefits to taking methylated multivitamins over standard multivitamins. Coupled with the potential for potentially severe adverse effects, it's not something you should do without good reason.

The second reason is that most methylated multivitamins on the market are extremely high doses. One example I found provides nearly 7,000% of your riboflavin, 2,500% of your B6, 1,200 percent of your B9, and a whopping 125,000% of your B12 intake. Normal versions of these vitamins don't impact your system much in megadoses because they're regulated by enzymes. Bypassing those enzymes and putting extremely high doses into your system in an active form has the potential to cause a lot of trouble in ways no one has studied.

Personally, my Microvitamin contains methylated folate and B12 at appropriate doses. I designed Microvitamin to be just enough to cover the gaps in an otherwise healthy diet and not as a workout supplement, energy booster, or other ultra-high-dose supplement.

My usual statement applies, of course: just because I take certain supplements does not mean you should as well. Always talk to your health professional directly and develop a plan that suits your unique health situation.

Sources:

1. Folate Health Professional Fact Sheet: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
2. National Cancer Institute Dictionary – Methyl Group: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/methyl-group
3. Science Direct - Methylation Overview: https://www.sciencedirect.com/topics/neuroscience/methylation
4. Assessing Effects of L-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial: https://pmc.ncbi.nlm.nih.gov/articles/PMC3869616/
5. L-Methylfolate as a Monotherapy for Treatment-Resistant Depression: A Case Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC7572139/
6. Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders: https://pubmed.ncbi.nlm.nih.gov/34794190/
7. Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health: https://pmc.ncbi.nlm.nih.gov/articles/PMC9380836/
8. Biochemical, physiologic, and clinical effects of L-methylfolate in schizophrenia: A randomized controlled trial: https://pmc.ncbi.nlm.nih.gov/articles/PMC5599314/
9. Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome: https://www.mdpi.com/2072-6643/11/3/608
10. The Role of DNA Methylation in Cardiovascular Risk and Disease: Methodological Aspects, Study Design, and Data Analysis for Epidemiological Studies: https://pmc.ncbi.nlm.nih.gov/articles/PMC4743554/