You’re Probably Taking Methylfolate Incorrectly. What To Do Instead:

Methylfolate has dramatically increased in popularity over the past few years. While most multivitamins and B-complex supplements used to contain only folic acid—the synthetic and potentially harmful form that I strongly discourage—many brands now include the so-called "methylated" form of folate instead. This shift is largely driven by the skyrocketing interest in MTHFR gene testing and the assumption that methylfolate is always better.

But is it really?

The Problem With the “Take Methylfolate and Fix Everything” Approach

MTHFR gene testing has become increasingly mainstream. People with variants in the two main MTHFR SNPs are often told they need to start supplementing with methylfolate immediately. The message is simple:

“You have a MTHFR mutation? Just take methylfolate.”

As a result, people follow the advice without question. But I believe this approach is flawed—and my position on this is clear throughout my work.

Even individuals with MTHFR mutations don’t always need to supplement with methylated folate. In fact, in many cases, doing so can cause more harm than good.

Still, the truth remains: some people do benefit from methylfolate. But the problem is:

They’re taking it in a way that almost guarantees they won’t optimally benefit—and might even feel worse.

High-Dose Methylfolate Is NOT the Solution

What happens when someone starts methylfolate, doesn’t notice a change, and tells their practitioner?

Often, the dosage gets increased. Sometimes up to 15 mg daily—which is far more than most people should be taking (virtually no one needs that much in a single dose).

This only worsens symptoms and—more importantly—distracts from finding the root cause of their health issues.

So, how can you take methylfolate the right way?

To answer that, you need to understand a little bit about how folate actually works in the body.

How Folate Works: Natural vs. Supplement Form

When you consume folate from food—think liver, leafy greens, legumes—your body converts it into its usable forms through multiple enzymatic steps.

Eventually, it goes down two primary pathways:

1. Purine metabolism (involved in DNA and energy production), and

2. Methylfolate production, which:

• Works with methyl-B12 to produce SAMe (the primary methyl donor in the body),

• Fuels neurotransmitter regulation in the brain.

The body regulates both of these methylfolate pathways very tightly. Why? Because:

• You don’t want methylation running too high,

• And you don’t want neurotransmitter synthesis to get thrown out of balance.

Why Methylfolate Can Disrupt the Brain

One of the most critical regulatory systems is in the brain, where methylfolate crosses the blood-brain barrier without needing folate receptors. This makes its entry into the brain very fast and potent.

That’s why flooding your system with high doses of methylfolate can overwhelm this regulation. It bypasses your body's natural "decision-making" process and pushes more methylfolate into the brain than it may need at one time.

This can lead to:

• Anxiety

• Irritability

• Insomnia

• Brain fog or overstimulation

In contrast, food-based folate is absorbed more slowly and converted gradually into methylfolate in appropriate amounts, allowing for natural regulation.

“But Isn’t Methylfolate Found in Food?”

Yes, it’s found in some foods—but the dose and absorption rate are completely different.

• Food-sourced methylfolate is present in micro amounts.

• Supplemental methylfolate is often 400–15,000 micrograms per serving.

• Food-based methylfolate is also released slowly, while supplements can cause a rapid spike in blood levels.

The Half-Life of Methylfolate Is Only ~3 Hours

Here’s something few people realize:

Methylfolate stays elevated in the blood for only about three hours.

That means a single high dose may only impact methylation or neurotransmitter production for a short window, after which the effects fade—and your body drops back to baseline or worse.

This leads to unstable methylation cycles and unpredictable brain chemistry.

The Right Way to Take Methylfolate (If You Need It)

To work with your body’s natural regulation, you want to aim for:

A steady, low-level supply throughout the day.

This mimics the body’s natural rhythm and helps avoid overstimulation or crashes.

Here’s how to do it:

1. Spread out microdoses every few hours

• Aim for 50–100 mcg every 3–4 hours

• Do not take it before bed—methyl donors can disrupt sleep

2. Ideal timing window: 7:00 AM – 4:00 PM

• Finish your last dose at least 4 hours before bedtime, bare minimum.

Practical Tips: How to Dose Low When Supplements Are Too Strong

Most methylfolate capsules start at 400 mcg or higher. That’s already 4–8x more than your ideal single dose.

Here are two workarounds:

Option 1: Use a liquid methylfolate supplement

• Determine exactly how much methylfolate is present per drop,

• Then spread your dosage over the day with precise control, based on the dosing and timing mentioned above.

Option 2: DIY dilute with a water bottle

1. Take a 400 mcg capsule and empty it into a 40 oz water bottle

2. Shake thoroughly to ensure full dissolution

3. Sip slowly throughout the day (ideally over an 8–9 hour window. Perhaps it’s the water bottle you take to work, so you can sip it over the course of your nine-to-five)

IMPORTANT: Be sure the powder dissolves fully—undissolved folate may settle at the bottom and deliver a large dose all at once at the end if not properly mixed.

But remember, this is not a recommendation to take methylfolate. Most people do not need it. You can read more about the different forms of folate in my Slow COMT Roadmap.

Have genetic results already? Get a supplement plan designed for you:

A note from Dr. Malek:

If you’re interested in helping support my work, please consider sharing my website. You can link my blog posts on your social media pages, reddit forums, etc. It’s not easy competing with multimillion-dollar healthcare behemoths, so your help in amplifying a relatively small voice really goes a long way. Thank you :)

~Dr. Malek

Keep in mind that this is not official medical advice. These are NOT recommendations; this is purely educational information. No doctor-patient relationship is established through this article or through any other information provided on this website.