If you don’t tolerate glycine, consider this deficiency.

Written By Malek Hamed, MD

This also applies if you don’t tolerate collagen and bone broth (which contain a lot of glycine), but there could be other reasons in those two cases.

Glycine is an extremely important amino acid involved in the production of connective tissue (hair/skin/nails/bones), detoxification pathways, sleep, and brain function. And almost everyone eating a modern diet is deficient.

I have personally been routinely recommending ~10 grams per day for years based on the research suggesting that it is not only conditionally essential (i.e. your body needs you to consume it in certain cases where it can’t make enough on its own) but massively underconsumed at the population-level.

This knowledge appears to have just gone mainstream. See, for example, Dr. Berg’s recent video recommending 10 grams of glycine per day, here.

The problem is that not everyone tolerates glycine very well. And as I’ve seen time and again in my own clinical practice, that includes people who actually need more of it for their bones, hair health, joints, detox pathways, sleep, and brain function.

What’s the cause of this?

There are two possible fundamental issues here:

(1) NMDA overactivation

and

(2) Oxalate toxicity

I’ve spoken about glycine and NMDA overactivation in my Roadmaps to Health membership. NMDA overactivation tends to manifest as:

  • headaches

  • light sensitivity

  • inner tension

  • sensitivity to soy sauce, MSG, and liquid aminos

  • sensitivity to glutamine supplementation (often taken for gut issues and athletic performance)

  • broad nerve pain

  • nonrestorative sleep

Glycine and oxalate toxicity, however, is a completely different issue. In these cases, the body is overloaded with a toxic molecule called oxalic acid/oxalate, and glycine can, in some specific cases, slightly increase the instantaneous load of oxalate and exacerbate symptoms.

Beyond kidney stones (which only happen in some cases of oxalate toxicity), oxalates can cause a very broad range of symptoms including:

  • chronic fatigue (from poor ATP production),

  • headaches,

  • joint pain,

  • inflammatory problems,

  • IBS,

  • on/off diarrhea,

  • post-exertional malaise (i.e. feeling really bad after any form of exertion including exercise),

    and much more.

Glycine has the potential to contribute symptomatically to both of these issues (without causing much real underlying harm). Where is the overlap?

NMDA overactivation and oxalate toxicity converge at vitamin B6.

Vitamin B6 in its active pyridoxal-5-phosphate form (P5P or PLP) is necessary for the conversion of glutamate (the brain’s main excitatory neurotransmitter) to GABA (the brain’s main inhibitory neurotransmitter.

Glycine can cause more glutamate-like activity if B6 is not sufficient or functional.

Vitamin B6/P5P is also necessary for proper metabolism of oxalates. A lack of functional vitamin B6 can lead glycine (among other things) to be funneled down the oxalate-producing pathway.

Very importantly, however, these issues are often not corrected by supplementing B6, which can indeed lead to toxicity (see my many blog articles on that). Often the issue is an assimilation/delivery/activation problem, which requires a little more nuance to correct.

The optimal approach is to:

  1. ensure that B6 activity is actually an issue through proper testing,

  2. then first address any and all issues that could be limiting the delivery and function of B6,

  3. and only then attempt low dosage, carefully titrated vitamin B6, using higher dosages only if necessary.

EVERYTHING in this article is purely educational and informational in nature. None of this is medical advice. Make no health changes based on this article. I am not your doctor. Discuss any and all implementations with your own doctor.

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If you don’t tolerate glycine, consider this deficiency.
If you don’t tolerate glycine, consider this deficiency.

This also applies if you don’t tolerate collagen and bone broth (which contain a lot of glycine), but there could be other reasons in those two cases.

Glycine is an extremely important amino acid involved in the production of connective tissue (hair/skin/nails/bones), detoxification pathways, sleep, and brain function. And almost everyone eating a modern diet is deficient.

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Hello all. Dr. Malek here. Because I’m aware that this article has the potential to be highly inflammatory, I have to caveat as follows:

  1. I have directly treated more B6 toxic patients than nearly any other doctor/provider in the world.

  2. I am an allopathic MD, i.e. a “normal” doctor. I’m not a chiropractor (though I have much respect for them) nor an ND, NP, healthfluencer, or anything else.

…

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I’ve personally encountered some skepticism, like the above, regarding magnesium glycinate and Slow COMT, namely that magnesium glycinate can actually worsen Slow COMT symptoms.

Grace…
Grace…
In this world of oil and steel…
In this world of oil and steel…

In this world of oil and steel, man is useful only insofar as he can fan the flames.

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Recently, the FDA under the Trump administration took an initial step towards officially recognizing potential harms of Tylenol (acetaminophen, also called Paracetamol) supplementation during pregnancy.

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Slow COMT is a biochemical variant that can profoundly shape mood, stress tolerance, and even how you respond to vitamins or caffeine. If you’ve ever felt “tired but wired”— exhausted in body yet racing in mind—or found that B vitamins and coffee make you jittery and anxious, the slow COMT gene variant is very likely the hidden key.

In this comprehensive guide, we’ll show you clearly what COMT is (and the famous Val158Met polymorphism), how to identify a slow variant in your genetic data, and, most importantly, how to optimize your lifestyle and supplementation to feel better.

We’ll also highlight what to avoid (yes, there are “healthy” supplements that can backfire for slow COMT-ers). By the end, you’ll have a reasonably clear plan for managing a slow COMT.

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Can You Get B6 Toxicity Without Supplements? And what causes it?

Yes, you can. B6 toxicity without supplements occurs when plasma pyridoxal-5′-phosphate (PLP) rises due to impaired metabolism, poor clearance, cofactor imbalances, subtle genetic deficits, insidious overconsumption, and more. And it’s much more common than most clinicians realize. This often leads to symptoms like tingling, anxiety, or autonomic dysfunction, even in the absence of any direct B6 supplement use. Here’s what causes it and what to do about it:

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Vitamin B6 is everywhere—multivitamins, B-complexes, prenatal supplements, even hydration powders. It’s recommended for everything from PMS to anxiety to neuropathy. But for a growing number of people, it’s making things worse.

Burning feet, vivid dreams, facial tension, and inexplicable panic episodes aren’t random—they’re often early signs of B6 overload. This isn’t a simple case of “too much of a good thing.” It’s a genuine biochemical derailment that can mimic everything from MCAS to mold illness.

In this article, I’ll walk you through the actual physiology of B6 sensitivity—why standard blood tests are misleading, why P5P (i.e. PLP) often worsens symptoms, and what it really takes to recover. This is for the people who were told B6 was safe and now cannot sleep, think, or feel like themselves.

~ Dr. Malek

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Dear Slow COMTer,

The goal of this roadmap is to give you the most direct, straightforward, actionable slow COMT plan possible.

If you've already run genetic testing (like 23andMe or AncestryDNA), you may want to confirm that you're carrying the COMT V158M variant, especially the homozygous (Val/Val) or heterozygous (Val/Met) form, though the latter is less of a concern unless you have symptoms associated with slow COMT.

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That’s a lot of B6.

Malek Hamed, MD

MTHFRSolve is my brainchild.

I’m an IFM-trained Functional Medicine physician with experience solving a wide variety of disorders still seen as mysterious by the modern medical paradigm.

I love solving those mysterious problems.

But doing so—I’ve found—requires two things that are, unfortunately, much too rare in our times: Authenticity and Depth.

MTHFRSolve is my way of giving you a little bit of that.

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Post-Partum and Post-Lactation Health Optimization