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BH4 and Neurotransmitter Synthesis

dopamine serotonin nitric oxide norepinephrine

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#1 AceNZ

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Posted 15 September 2018 - 11:27 PM


BH4 (tetrahydrobiopterin) is a co-factor required for the production of many neurotransmitters, including dopamine, norepinephrine, serotonin, melatonin and nitric oxide (NO).

 

The diagram below shows how BH4 is used:

 

Phenylalanine --> Tyrosine

Tyrosine --> L-Dopa (precursor for Dopamine, Norepinephrine and Epinephrine)

Tryptophan --> 5-HTP (precursor for Serotonin and Melatonin)

Arginine --> NO

 

When BH4 is used in those reactions, it becomes BH2 (biopterin).

 

BH2 is then recycled to BH4 by a process that requires SAMe and methylfolate.

 

An additional, and very important, aspect of this biochemistry is that BH4 is easily damaged by oxidative stress, also known as reactive oxygen species (ROS). ROS can increase as a side-effect of many health problems, ranging from inflammation to being overweight.

 

Understanding what BH4 does and how it works and how it can be damaged suggests the following approach may help some people correct their neurotransmitter levels:

 

1. Reduce ROS using a combination of anti-oxidants and anti-inflammatories. The specifics depend on your individual condition, lab tests, sensitivities, and so on. High-dose Vit C probably isn't a good idea here, since Vit C is a co-factor in breaking down several neurotransmitters.

2. Remove any and all Folic Acid from your diet. Folic Acid isn't found in nature, and it mucks with folate metabolism.

3. Support your methylation pathways, which drive both methylfolate and SAMe. This is a complex subject, and sadly there's a bunch of misinformation floating around about it. In very broad terms: make sure you're getting enough B-12 and green leafy vegetables. Supplement with methyl-B12 (first) and methylfolate (after a few weeks or so), if required (a minority may need to start with adenosyl-B12 or hydroxo-B12). On the methionine processing side, make sure you're getting enough magnesium, since Mg is required to produce SAMe.

4. In the near term, while you're working on the above, you might also try supplementing the post-BH4 products, Tyrosine and/or 5-HTP. Tyrosine still needs one BH4-dependent step to get to L-Dopa, but that's better than the two steps needed when starting from Phenylalanine. Just be aware that as your metabolism improves, you should be prepared to taper back.

 

It's worth mentioning that low or ROS-damaged BH4 may explain why some people don't notice any changes when supplementing Phenylalanine or Tryptophan.

 

Although BH4 is available these days as a supplement, I'm skeptical about its value. If your ROS are high, BH4 will be destroyed after ingestion, and the byproducts there don't do anything good. In addition, since it's easily damaged by oxidation, packaging and so on would have to be done very carefully; bare powders seem unlikely to avoid oxidation. The high cost involved for adequate dosing is also an issue.

 

SAMe can also be supplemented directly. However, high levels of SAH, the downstream metabolite of SAMe, can inhibit literally hundreds of enzymes. A little further downstream, high levels of homocysteine are a significant cardiac risk factor. So, much better to work from a diet perspective, by making sure you're getting enough methionine (easy unless you're a vegetarian) and Mg. Having said that, a *short* trial of SAMe might be useful, from a purely diagnostic perspective.

 

 

 

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#2 John250

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Posted 16 September 2018 - 06:37 PM

What if your MTHFR genes show you should avoid methyl donors? Then SamE wouldn’t be an option right?

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#3 AceNZ

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Posted 16 September 2018 - 07:35 PM

What if your MTHFR genes show you should avoid methyl donors? Then SamE wouldn’t be an option right?

 

It's risky to treat based on SNPs alone. Mutations aren't always fully expressed, and even when they are, there can often be offsetting factors.

 

The MTHFR risk alleles have the potential to slow down the MTHFR enzyme, which in turn can theoretically cause low methylfolate (MTHF) and high homocysteine (Hcy) , which is bad. If you have high Hcy, then supplementing SAMe would be bad. However, with high Hcy, supplementing methylfolate (another source of methyl groups) would be good.

 

IMO, SAMe is only useful in two scenarios: one is if you have low Hcy and adequate, well-established Mg and Methionine intake. The other is as a short trial only, to see if increasing methyl groups helps you feel better. If it does, then that's good evidence that there are other things to work on.



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#4 John250

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Posted 17 September 2018 - 07:11 PM

It's risky to treat based on SNPs alone. Mutations aren't always fully expressed, and even when they are, there can often be offsetting factors.

The MTHFR risk alleles have the potential to slow down the MTHFR enzyme, which in turn can theoretically cause low methylfolate (MTHF) and high homocysteine (Hcy) , which is bad. If you have high Hcy, then supplementing SAMe would be bad. However, with high Hcy, supplementing methylfolate (another source of methyl groups) would be good.

IMO, SAMe is only useful in two scenarios: one is if you have low Hcy and adequate, well-established Mg and Methionine intake. The other is as a short trial only, to see if increasing methyl groups helps you feel better. If it does, then that's good evidence that there are other things to work on.


My Hcy is on the lower end and I supplement with a good amount of magnesium. I’ve never supplemented with Methionine though.





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