Ammonia overload seems to be quite common in ASD kids yet also surprisingly little known.
Please, please note this well: Testing for ammonia is completely unreliable: Ammonia levels vary hugely and rapidly hour by hour. If you happen to test when it's high, then yes, you've confirmed an excess. But it is very easy to miss the point when it's high because the level goes up and down so quickly and often. So you may happen to test when it's low and mistakenley think there's no problem.
Note; We did not think we had an ammonia problem until we tried prospectively supplementing with Citrulline and even then, we might have missed the behavioural change. It wasn't until we then tried supplementing with AKG that we smelled the ammonia (very strongly!) and then suddenly got a very large change in his behaviour.
It's also often fairly easily managed (though of course, some cases are far harder than others).
Don't want to read all this?
Just buy the L-Citrulline and AKG and try them! This could be a simple and low-risk game changer.
And/or get probiotic strains BB536 and HU58 (see below) to attempt to fix the problem.
And/or try digestive enzymes (Digest Spectrum is likely the best as it has DPP IV activity but build up to the dose slowly!)
There are tests for Ammonia however they only show when someone is in real trouble, at the very time of the testing. It's quite possible to be in trouble on an ongoing basis but for it not to be showing up so easily in testing. How do I know? Because we've seen exactly this.
It tends to show up as "the sillies"; constant drunken laughter which can then turn aggressive. Lack of focus, "brain fog" and, in extreme situations, seizures. So I think it's likely that it's often confused with Candida overgrowth.
This page is certainly not meant to be comprehensive, just a good starting point to learn more and a quick summary of how you might prospectively try dealing with it, to see if it's a problem.
There are plenty of articles out there on this but here are a couple of good resources:
A very good talk at AutismOne by Maria Janik (who has kindly reviewed this page for me):
There's a great document going into details around the above talk, in the Recovering Kids Facebook group:
Great articles on this site:
Note: Alex Zahrakis mentioned in a post on Ammonia that night-wakings are well documented to be a symptom.
https://www.facebook.com/groups/1097163307452157/posts/1316817475486738/
He also mentions Ornithine as a supplement but we didn't see anything from it (We tried: https://naturesfix.co.uk/product/l-ornithine-500mg-60-caps-douglas-laboratories/ )
That's a complex thing BUT it is almost certainly driven by the gut.
I don't have a complete answer here but the absolute most effective thing we've found for reducing it is the use of spore forming probiotics.
The mixture of strains found in MegaSporeBiotic has been shown to reduce ammonia but I can't find evidence for any of the strains alone apart from the HU58 (which is sold by the same company as a single strain, high potency product).
I would start using HU58 (or MegaSporeBiotic which contains HU58 and has good evidence for reducing ammonia).
Also, Bifidobacterium longum BB536 has been shown to markedly reduce ammonia production in the gut.
I would start using BB536 (or this which is 1/5 of the strength but has not Calcium carbonate).
Although it can become very involved, and there are several different ways you can reduce excess Ammonia, it seems that almost everyone can at least see an improvement, and therefore get an idea if it's a problem at all, with some very basic supplementation. However, longer-term it's likely that you need to improve gut health to really make a difference.
L-Citrulline
AKG
Pteridin 4 (used to be sold as "BH4")
Ornithine (this did nothing for us but for some it can be very good)
Adeno B12
Royal Jelly
L-Citrulline
The first thing to try is L-Citrulline. Which is a simple amino acid.
It helps process out the excess ammonia.
I don't think there's much to choose between any particular brand on this however the iHerb own-brand version seems good:
Now Foods L-Citrulline:
Capsules: https://www.iherb.com/pr/now-foods-l-citrulline-750-mg-90-veg-capsules/6688
Pure powder: https://www.iherb.com/pr/now-foods-l-citrulline-pure-powder-4-oz-113-g/15501
We started with what Janik recommended; 250-500 mg (1/2 to 1 cap of the above). That usually at least lets you see if the sillies calm down. It did for us. Probably not more than 1000 mg (which we've certainly used often).
Note: The Jarrow Formulas version also has a methylated B9 (folate) added. Many of our kids respond really badly to methylated vitamins so I would avoid that.
Also, too much can cause an upset gut.
AKG
For some kids, Citrulline may be all they need.
For us, Citrulline worked well for a while then the effect appeared to wear off. So Janik's next suggestion is to supplement with Alpha Ketoglutaric Acid (AKG).
Dose, for us, has been about 300 - 450 mg. But it's a matter of trying and seeing what symptoms you see. And note that Glutamate connection, below!
Note: There is confusion regarding AKG converting to Glutamate (excitory neurotransmitter). It does this if there is excess AKG. If the AKG is being used to remove Ammonia, it's not going to be a problem. However it's worth knowing that more is certainly not always better. Bear in mind that AKG has been life changing for us and other parents I know.
Kirkman brand AKG:
https://www.iherb.com/pr/Kirkman-Labs/58317
Klaire Labs brand AKG:
https://klaire.com/v135-06-alphaketoglutaric-acid
Seeking Health brand AKG (on an EU site)
https://mass-zone.eu/en/seeking-health-alpha-ketoglutarate-akg-60-vegetarian-capsules-p-2651.html
Pteridin 4
Sadly this product is apparently being discontinued but you might still be able to find it?
The above worked pretty well but then our doctor suggested trying Pteridin 4.
This works extremely well for processing out excess ammonia but it is not cheap at all and it must be sent chilled, so it's not available everywhere.
We get it from Spectrum Supplements (AUTISM-EU gets 10% off the EU site. I assume using UK, CA, COM works on the others but haven't tried):
Pteridin 4, UK: https://www.spectrumsupplements.co.uk/supplement/tetrahydrobiopterin-60-capsules/
Pteridin 4, UK: https://naturesfix.co.uk/product/bh4-pteridin-60-caps-ecological-formulas/
Pteridin 4 , EU: https://www.spectrumsupplements.eu/supplement/tetrahydrobiopterin-60-capsules/
Pteridin 4, Canada: https://www.spectrumsupplements.ca/supplement/tetrahydrobiopterin-60-capsules/
Pteridin 4 , USA: https://www.spectrumsupplements.com/supplement/tetrahydrobiopterin-60-capsules/
Pteridin 4 USA only: 10% off for first-time orders dcAHUM928 https://www.holisticheal.com/pteridin4-2-5mg-60-caps-formerly-called-bh4.html
NOTE: We have since found that a combo of both the L-Citrulline, AKG and Pteridin 4 seems to give the most benefit.
Ornithine
It did not help here but according to Alex Zharakis (and Maria Janik now mentions it) it can be very useful.
Adeno B12
It must be the Adeno form! Methylated will not do it. In fact, according to one parent commenting in Maria's group, you must use a pure Adeno, (for example the Seeking Health Adeno B12) not a mixed Adeno/Hydroxy. However we have certainly seen huge improvement in ammonia symptoms (and so has another parent) with Pure Encapsulations Adeno/Hydroxy B12 (we also found it good for sleep).
Maria Janik has said that a 1000 mg single acute dose of pure Adeno is needed but we seem to find that ongoing dosing at roughly 500 mg is good (hard to know exactly, we use part of the Pure Encapsulations Adenosyl/Hydroxy B12).
Royal Jelly
This apparently can stimulate BH4 production. I've not used it but know another parent that saw success with it regarding Ammonia symptoms.
AKG acts as a nitrogen transporter but it can also be used up in another metabolic process (to do with inflammation) and therefore you can end up with too little of it to transport adequate nitrogen (Ammonia).
Work up slowly, across several days to a couple of weeks or more. It's hard to know how much is needed and I am no expert in this. I know Janik said often 1/2 cap works but a full cap may be needed even in a smaller child. But it's a matter of working up, till you get what appears to be symptom resolution. Hold there for some time (two or three months) and then slowly titrate down again to see if less is now required. For us, we've needed a full cap of all three at times.
Also, if you are doing things to decrease inflammation (which you probably should be!) then it's likely that less will be required due to that.
Note that Janik says you don't want to be pushing Citrulline too hard if you are using AKG since you can "imbalance the Urea Cycle and there will be too much Citrulline turning into Arginine Synthase".
For us, the AKG really, really worked!
We had very, very Ammonia smelling nappies and eventually the sillies calmed down. See below.
Also, beware of too much meat, fish and egg white because protein drives Ammonia and we've found we can overload him (well, his gran's delicious meatballs mean I can overload myself!).
Giving Yucca root with high protein meals can apparently help avoid that a lot but we've not tried that.
Maria says that there's no particular timing but giving with higher protein meals, and giving a bit more if there's an unusually high protein meal, is fine.
We saw some improvement with the L-Citrulline but then the effect appeared to wear off.
We may have dismissed it but I am so glad that we didn't.
We tried a little AKG... and the sillies got slightly worse for a couple of days... then his nappies started to smell of Ammonia. Then they began to really stink of ammonia.
We slowly ramped from about a tenth of a cap of AKG, through to about six tenths, across about two weeks. The smell of Ammonia was overpowering. Then, it stopped. And he calmed way, way down. The sillies stopped and he seemed more "with it".
However, he got worse when we backed off for some weeks (because it was simply hard to hide).
Then our doc suggested the Pteridin 4 and we started to force the issue with taking supplements (basically, take them or no breakfast). That has made a huge, huge difference to all our lives! The difference when he is on all three is stark. Less anxious, less silly, less aggressive. Easier to settle. Better sleep. Easier (possible!) to get back to sleep if he wakes.
A "workaround" is something which stops a problem manifesting without necessarily stopping ("fixing") the root-cause of that problem.
Yes, fixes are certainly preferable but since finding out what the root-cause of a problem actually is can be extremely difficult and take a very long time, it can often be very valuable indeed to use a workaround to allow us to cope with the really obvious and deleterious effects of the problem in the meantime.
They simply supply more of the raw material that is needed for ammonia transport. If someone is inflamed they can be shunting some of the AKG into a different pathway (Quinolinic acid, I believe) instead of using it for ammonia transport. Supplementing doesn't fix the upstream problem of the chronic inflammation or give any clue as to what's driving it (though I'd bet it's gut mediated!) it only prevents the downstream problem of impaired ammonia clearance which then brings further problems (manifesting as "the sillies" and aggression).
No, there is no specific food that drives ammonia, only a macronutrient; protein. And everyone needs protein, especially children. Protein is not the problem. Excess protein may worsen the problem. Which is excess ammonia, caused by too little AKG, caused by chronic inflammation, caused by... Chronic infection? Gut Dysbiosis? Heavy metal toxicity? The list goes on and, each one of those may have yet another upstream cause.
No, the supplements are not prescription. They are just simple supplements.
They are best given with food. Probably best to start with Citrulline. Beware when combining them since you can overdo supplementation.
From: https://www.verywellhealth.com/the-benefits-of-alpha-ketoglutaric-acid-89402
"Alpha-ketoglutaric acid is considered safe and well-tolerated. Studies investigating the effects of alpha-ketoglutaric acid reported few adverse symptoms after three years of use. As a compound made from non-essential amino acids, alpha-ketoglutaric acid is not a substance on which you can readily overdose. Any excess in the body will either be excreted in urine or broken down into the basic amino acid building blocks for other purposes."
Many reasons. Here're some:
AKG is a normal part of metabolism and can be turned into something which is used in ammonia clearance. But it can also be turned into quinolinic acid - which is done as part of the primary inflammatory response (which is meant to stop within a couple of days).
Quinolinic acid is extremely cytotoxic (it kills cells - hence, primary response - not antibody mediated - scorched earth approach).
It's thought to be particularly used against pathogens in the brain (I assume it therefore tends to be concentrated there?). Being cytotoxic, that's really not good for the brain cells, of course. So that's not great since our kids seem to end up having the primary immune response turned on chronically.
So, if someone is "inflamed" (generating a primary immune response) they're likely shunting AKG into quinolinic acid.
However, that leaves less AKG for ammonia clearance. Hence, ammonia build-up. Hence more AKG gives more substrate to be used for ammonia clearance (or more Citruline, I can't remember how it all relates now...).
So, turning off the primary immune response should fix that setup. And, yes, mould exposure can turn on the primary immune response, hence mould exposure can lead to excess ammonia.
Ammonia is also directly generated by bacteria in the gut. So having a dysbiotic gut could be generating ammonia directly. As well as causing immune dysregulation, which itself could be keeping the primary immune response turned on. We see this: If he's constipated, he gets major ammonia symptoms which clear within a few minutes of him finally having a big poo (remember that ammonia levels fluctuate rapidly).
Apparently H. pylori is a primary producer of ammonia: It produces an enzyme called urease, which catalyzes the conversion of urea (a compound that is normally present in the stomach) into ammonia and carbon dioxide. Asmentioned by Dr Izabella Wents at [01:35:24] here https://www.betterhealthguy.com/episode184
I'm quite sure there are other sources (examples from a friend of mine: Aluminium impairing NOS, poor methylation).