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GAD1 Mutation and Glycine Supplementation

I heard you should not supplement with Glycine if you have high Glutamate and low GABA. According to my DNA, I am homogeneous in several GAD1 SNPs. It says that I have low GAD1 activity and have high glutamate and low GABA.

I have been supplementing with Glycine and Magnesium Glycinate before bed. I haven’t found either to be a problem and the magnesium glycinate has actually been beneficial. I don’t seem to get an effect from Glycine though. I do take them with Taurine, which DEFINITELY has been beneficial to me. Tryptophan is very helpful as well.

In the past I have also supplemented with GABA directly. Sometimes it would work, other times it caused anxiety

So are those genetic tests reliable? Additionally I am a Type 3 in the neurotyping system.

Which test is it?

Textbook type 3… here is what it looks like from a neurotransmitters perspective:

The magnesium taurate (and taurine) will help because it’s effective at increasing GABA. GABA by itself is extremely hit or miss because it is very inefficient at passing through the blood-brain barrier.

Tryptophan will help because it raises serotonin. It is even more effective when combined with B6 (P-5-P form) and 5-HTP (5-HTP is not super effective).

SAM-e can also be a life saver. Type 3 (and 1A) are undermethylators. Because of that they don’t produce much serotonin and acetylcholine and don’t clear adrenaline efficiently. SAM-e is the end-product of the methylation cycle, it can thus help compensate for the poor methylation.

Thanks Christian!

Just a standard DNA profile that you can get through a company like 23andMe. There are a few SNPs associated with the GAD1 enzyme. You can also see the ones for COMT as well.

These are not reported by 23andMe. You have to dig into the raw DNA data. It’s not that hard to do though. You just need the rs numbers, which I can give you if you need them.

Proteine powder and glycine can be mixed ?

Interesting. After seeing this and one of your other forum posts about the 2B subtypes, I wonder if I am a “2B confident” instead of a Type3. My DNA results show I am a mix for COMT. Is there any easy way to tell the difference?

I think Glycine works best on an empty stomach. I never mixed Glycine with protein powder, so I don’t know.

I prefer to consume glycine by itself first, then the protein 15-20 minutes after

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Why is 5-HTP less effective than tryptophan? Does it get converted in the periphery too much?

It’s more that moderate/long-term use of 5-HTP by itself can lead to problems. Depleting the catecholamines. And it can also lead to a paradoxical response (activating you and increasing anxiety) by lead to too much serotonin. In that case the body responds by increasing cortisol and adrenaline levels.

I prefer to use much smaller doses of 5-HTP with some tryptophan.

You might find the following paper interesting:

Synthesis of serotonin from 5-HTP and dopamine from l-dopa is catalyzed by the same enzyme, L-aromatic amino acid decarboxylase (AAAD). Dopamine and serotonin amino acid precursor administration must be in proper balance. If only 5-HTP or 5-HTP that dominates dopamine at the enzyme is administered, it will block dopamine synthesis at the AAAD enzyme through competitive inhibition, leading to depletion of dopamine and the rest of the catecholamines.6,9,12,15,30

Metabolism of serotonin and dopamine is catalyzed by monoamine oxidase (MAO). The activity level of MAO is not static. With increasing doses of 5-HTP, which lead to increased serotonin levels, MAO activity increases. Without a properly balanced increase in dopamine there will be increased metabolism of dopamine leading to depletion"

I tried 5-HTP for a while. It always made me feel weird. I prefer Tryptophan.

I also heard once that Tryptophan actually is more likely to increase serotonin levels in the brain (where we want it) because 5-HTP is converted into serotonin too rapidly elsewhere and serotonin, unlike Tryptophan and 5-HTP, can not cross the blood brain barrier. Not sure if that is true, but regardless I find Tryptophan more effective.

That’s indeed very interesting!

It seems to be the case with chronic usage. As I understand it, usage once in a while when one’s agitated or nervous is fine, long term chronic use leads to problems. The same holds true for L-Dopa in Parkinson patients, long term L-Dopa use leads to on-off-fluctuations. It’s another mechanism but there is definitely a trend with these substances that have a direct nearly uninhibited impact on the CNS.

That is 100% accurate.My friend William Wallace (best name in the industry by far), a Ph.D. in neurochemistry, told me the exact same thing

So is 5-HTP something, even as a Type 3, should not be taking anymore? Currently I am taking 5-HTP throughout the week and then I don’t take any or most supplements on the weekends. Thoughts?

The approach I find to work best is taking it 1 day on, 1 day off… or 2 days on, one day off. And I would recommend a low dose tyrosine on the “off” days to avoid dopamine depletion. A serving of Power Drive would work well.

In light of new evidence I personally prefer a combo of low dose 5HTP and tryptophan.

The 5-HTP I currently have is 200mg. Is that low dose or are you talking even lower than that? And what dose of Tryptophan have you found works best?

I take a 1 gram of tryptophan before bed. Sometimes I take another gram in the middle of the night if I wake up and have to use the bathroom. Works for me.