The potential benefit of the ketone
BHB in autism was covered extensively in earlier posts. It looks like different people may benefit
for entirely different reasons and some may not benefit at all.
Some MCT oils, taken as precursors to BHB, can actually make people worse.
Some MCT oils, taken as precursors to BHB, can actually make people worse.
Measuring ketones and
glucose in blood
Click for a summary of the previous posts.
I know that
some readers of this blog have found that BHB/C8 does indeed provide a benefit
in their specific type of autism. The
benefit seems to vary, but given all the biological modes of action of the
ketone BHB that is not surprising.
Increased speech is a frequently noted benefit.
My initial
combination of Ketoforce plus C8 continues to be effective.
Substituting
a cheaper MCT oil containing both C8 and C10 (Bulletproof XCT oil), was less effective and after a
matter of weeks produced a negative effect. It appears that C10, after a while,
can produce mild anxiety and agitation in some people. In our case this goes
away when stopping the C8+C10 MCT oil and then reappears restarting it.
When it
comes to C8, it appears that not all food grade 98% C8 products are actually
what they claim to be. This is a recurring theme with all supplements, they
lack the quality control you get with pharmaceuticals.
Our reader
Yi did at one point raise the issue of BHB causing diuresis. We also
experienced this and much more so with the “mixed” C8+C10 MCT oil, rather than
the “pure” C8.
The
combination of increased diuresis and all the sodium, magnesium, potassium in
the BHB salts may very well create an issue with electrolyte levels. Potassium
does seem to be the most critical one to monitor.
Different
BHB products contain very different amounts of sodium, magnesium, potassium and
so it is unwise to simply substitute one for another.
Our reader
Agnieszka did experiment with different BHB products and found that, based on
urine testing, Ketoforce was the most effective. I also think this is likely
the best choice. Ideally you would measure BHB in blood and devices are available (see above photo).
For people
living in Europe, BHB products have fallen foul of EU legislation that requires
new supplements to be approved before they can be sold in the European Union.
As BHB is a recently introduced supplement, it cannot legally be sold in the EU
until someone pays for it to be approved. This means that in EU countries that strictly
apply the rules, like the UK, you cannot buy BHB, but in other EU countries you
still can.
The same
legal status regarding BHB in the EU also applies to Agmatine.
Another
oddity is that Melatonin is banned as a supplement in the UK, but not other EU
countries; it is a very popular supplement in North America.
Peter, your posts were v. helpful for the whole family on the ketones series in different reasons (e.g. caprylic acid helps Mom to sleep better as evidence by fitbit numbers, caprylic acid gives college age daughter more energy) For the Nicotinamide Riboside, would you expect behavioral changes for an asd child? Or if mitochondrial dysfunction, would you expect to see longer term correction on energy, reduction of impairment in mitochondrial areas in the brain, etc? Can you explain what you think benefits would be short and long term for an asd teenager?
ReplyDeleteThe potential benefits of Nicotinamide Riboside relate to NAD+, which plays a role directly and indirectly that might help someone with autism.
DeleteThere could be an anti-inflammatory effect via CtBP, as proposed in Part 4 of the blog series.
https://epiphanyasd.blogspot.com/2018/09/ketones-and-autism-part-4-inflammation.html
There could also be a benefit to mitochondrial function in someone with mitochondrial disease.
I would imagine that the potential benefits would be short term and so you would have to keep taking this quite expensive supplement.
In many people with autism, all kinds of inflammation cause a worsening in their symptoms, so it might be increased anxiety, stereotypy etc. So these symptoms might improve.
Our reader Tyler is a fan of Nicotinamide Riboside and has he has looked into it in detail.
Hi Peter,
ReplyDeleteOne thing I did not manage to resolve last year is to optimize the dose/ingredients of ketone treatment. Did you try to use BHB only - to compare the results with BHB/C8? Or C8 only? Also, can you see long term stability of the effects? I feel like it decreases, at least in myself. This is in line with what was found in a small study on BHB in refractory migraine here:
https://healthdocbox.com/Headaches_and_Migraines/97413427-Abstracts-of-the-18th-international-headache-congress.html
Abstract no: PO-01-069
"benefit from bHB seemed to coincide with a drop in average peak bHB blood levels from 0.62 mmol/l to 0.3 mmol/l after 1–2 weeks of ingestion."
How to deal with this? I wonder if you or anyone here tried intermittent dosing approach? Like it is sometimes done in ketogenic diet for weight loss (with one day a week of "ketosis freedom") or on in Prof. Evangeliou's research on KD in autism?
On a different note, this is what I found today:
"Cheap common drugs may help mental illness".
https://www.bbc.com/news/health-46809517?fbclid=IwAR2BHlWlDApj2Adx-ecZPQnUvSzY9vVhAyjBAqtLiyJlYaMYx9mjnPFOhAo
"The team focused on:
-anti-cholesterol drugs called statins - which may calm inflammation linked to mental health problems or help the body absorb anti-psychotic medications
-blood pressure drugs - which may alter the calcium signalling in the brain that has been linked to bipolar disorder and schizophrenia
-type 2 diabetes drug metformin - which may alter mood
But rather than test them in trials, the scientists went looking for evidence in the real world."
"The researchers at University College London say their findings have "enormous potential"
I will purposely not copy here the sceptic comments at the end of the press release.
Agnieszka, the study is interesting and as we both know:-
Delete"Cheap common drugs do help some autism"
I am still experimenting with BHB/C8 and now have a large supply of materials. I will only now use KetoForce for BHB and "pure" C8. No more C10 or mixed BHB powders.
My next step is to use 20ml C8 twice a day.
I think what is likely needed is a short spike in BHB levels rather than a very low uniform level. Some others think a small dose of C8 taken several times a day might be best.
If possible it would best to find a solution using just C8, since then there is less problem with electrolytes and also it should be cheaper. My earlier reading suggested that 20ml of C8 should be similar to 10ml of KF. So perhaps all my case needs is 40ml of C8 a day.
I think making short pauses in BHB/C8 is a good idea.
Peter,
DeleteWhy do you think a short spike is what matters? Do you mean any specific mechanism of action?
I forgot to add that KetoOs were as effective as KetoForce in raising ketones, at least per acetoacetic acid Keto Diastix readings. At times I tried various brands KetoOs products had dairy ingredients so it was a no-go for a child with milk allergy.
Agnieska, I think in people whose mood improved with BHB the mode of action is HDAC inhibition leading to ramification of microglia, described in the paper below that I highlighted in in of my posts.
Deletehttps://www.ncbi.nlm.nih.gov/pubmed/29058362
That would suggest that other HDAC inhibitors might have the same effect in mood in those people.
I think some of the modes of action we have found for BHB will require a certain concentration in the blood to be triggered, but may well last longer than the duration of the spike.
All we get from a single daily dose of KF/BHB is small spike in BHB that last an hour or so, but the effect seems to last all day.
Peter,
DeleteI see that you are thinking maybe pure C8 only- sans BHB supp- may be the only necessary piece. But what level for your case are you at on the KetoForce BHB dosage? Thanks in advance.
LS, my fall back position is 10ml of Ketoforce and 20ml of C8. It appears to me that with 40ml of C8 you could achieve the same level of BHB in your blood. This could be studied in healthy adults and measure BHB in blood samples, whereas I am just "guessing".
DeleteUndoubtedly, C8 will have effects other than just producing BHB, and that might limit the dose you would want to give.
Currently it is just a case of seeing what works best in that particular person.
At last - we are trialling Bumetanide, 0.5 mg twice daily.
ReplyDeleteIt's about 20 days into this, and my kid is now sleeping very efficiently. Sleep is deep and shorter than usual, which means early mornings. With 2 * 100mg potassium the last blood draw looked perfect, and I will slash that in half until next blood draw in two weeks to see if there is a big change or not.
I have a question. Can I assume that the bumetanide is working since sleep is affected? I don't see any cognitive effect at all yet, and I plan to do 2-6 weeks more (The amount I have won't last more than 60 days).
It's usually best to try one thing at a time, but given how little Bumetanide I have I wonder if I should use the last months supply together with something aimed at upping NMDArs? I remember one previous reader who got results only by a combination of GABAa and GABAb-acting drugs. I would appreciate any advice on the subject.
Best regards,
A very regular reader, this time anonymous
Since potassium loss is not an issue and you want a definitive answer, I would change your dose to 1mg for the first daily dose and 0.5mg for the second.
DeleteIn my case 0.5mg twice a day did not do much. 1mg once a day was much more effective.
Thank you, that sounds like a good plan!
DeleteHi Anonymous,
DeleteWhen you say he’s now sleeping better, how was he before you started bumetanide?
Sleep was good/ok before. We use melatonin at bedtime, not sure it is needed actually. Waking up in the middle of the night sometimes, perhaps 2-3 times a month.
DeleteNow it is more like less sleep is needed, and sleep is so deep that it doesn't matter if we co-sleep or not. Waking up at 4 o'clock and ready for a new day!
So, sleep is worse for us parents, but better for our kid.
Hi Peter!
ReplyDeleteThanks for this recent post. I had been taking a pure C8 oil for several months (expensive), and felt quite good on it.
Then I ran out and purchased a cheaper C8+C10 combo. I noticed a distinct increase in moodiness and anxiety shortly after this switch, but did not connect it to the switch in the oils.
I am interested in trialling the BHB, but cannot find what you have recommended in the past. Is this a powder or a liquid?
I struggle to observe/evaluate what I am feeling/experiencing when I introduce or change up supplements. I feel I am not observing myself accurately.
Cheers.
The BHB I am using is called Ketoforce and is a liquid.
Deletehttps://ketosports.com/ketoforce.html
It is not cheap, but is one of the better products.
Here is some very interesting new research I meant to post several days ago concerning ketogenic supplements and seizures, but my phone hiccuped on me:
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2019/01/190108125511.htm
Paper:
https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.13961
So in a model of seizure induced activity from hyperbaric oxygen (high levels of oxygen can be toxic and too much induces seizures) they found that rats given a 70% carbohydrate diet had their seizure threshold increased (i.e. more tolerance to seizure induced stress) via ketogenic supplements. The combination that seemed to work the best was supplemental hydroxybutyrate and MCT Oil (NOW Foods Brand which I believe is mostly if not all C8).
This is very important research because it shows that supplemental ketone supplements may be able to address seizure conditions and conditions which tend to be comorbid with seizures such as autism, without the need for a strict ketogenic diet. The research also may give some hints as to the optimal dietary approach using ketogenic supplements as well.
Here is another paper I meant to post a few days concerning histamine and long-term memory:
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2019/01/190108084422.htm
Paper:
https://linkinghub.elsevier.com/retrieve/pii/S0006322318320213
The gist of the research is that it was found that boosting histamine levels in the brain via a drug called betahistine mesilate facilitated long-term memory retrieval for any memories greater than 48 hours. The research was conducted on both mice and humans.
Now what is relevant here to autism besides all of the discussion about histamine in past blog posts of Peter's is that the mechanism of action for pro-histamine treatment in boosting long-term memory is a neuroscience concept known as stochastic resonance which means that if you have a series of low amplitude and below detection threshold signals, you can raise those low amplitude and below detection threshold signals by adding random noise which on average raises the amplitude of all signals and thereby causes the below detection threshold signals to rise above the detection threshold. If too much noise is added, then aberrant and unwanted random noisy signals will be detected.
In autism, there is strong evidence for excess noise in the brain, especially in the visual cortex where some people with autism may experience a phenomenon known as visual snow, which is in effect the result of excess noise in a part of the brain called the lingual gyrus (has nothing to do with language). Visual snow is tantamount to if you were to take some of the static from a television in the pre-digital era and dial it a channel from which no station was broadcasting and then put some of that "static" in your visual view.
What this shows is that while high levels of histamine may be good for long-term memory, it is not inconceivable that too much of it may be responsible for these "noisy" side effects in the brain.
Hi Peter, do you know about low dose immunotherapy? What could I try? My son is having OCD behaviour,clicking tongue and hysterical laughter at the same time.
ReplyDeleteValentina
Valentina, you could ask your doctor for 5 days of prednisone, like 40mg a day. This is a steroid, but short term use is safe and if you give it early in the morning (well before 9am) you further reduce the impact it has on the body's own hormone production. Short term steroid use does not need a gradual tapering of the dose.
DeleteWhen Monty has a PANS-like episode with sudden onset vocal tics, this solved the problem.
Thanks Peter, I have prednisone 20 mg from my daughter and will use it, 2 tablets at 8 am.
DeleteValentina
Peter, do you think a Cunningham or Anne Connolly panel useful for our kids? I will do the Cunningham next week for more extensive reasons, but don’t know about the Connolly... Since you mention PANS.I have to do something right now since my kid is at yhe same time getting better in so many areas but increasing stimming (hand posturing and visual stims), OCD tendencies and vocal stimming. I have had enough if blindly stumbling around and trying stuff and since she is also getting better all the time, I am a bit stumped. In many parent groups the answer to why this is happening is mostly increased yeast issues (and many of them have incredible success with antifungals) but that is a rabbit hole since yeast can be an issue in many bodies but if you go chasing it like mad, with nystatin diflucan macmiror etc you can end up insulting the detox organs in the body so much that whether there was yeast to begin with or not, you can cause disbalance overall, so at this point I am not inclined to just hop on that train.
ReplyDeletepe to, there is no harm in running these tests. They might tell you something conclusive, they might not.
DeleteI think there are many reasons why someone's autism is variable, it is well worth figuring out what affects a particular person. Copying other people may take you in wrong direction and this is very easy to do.
Peter are there drugs or supplements that have similar mechanisms of action just like Roflumilast (and work like Roflumilast) in enhancing cognition? Also, have you tried clemastine yet and have seen any improvements?
ReplyDeleteIbudilast looks like the most promising equivalent, but nobody is researching its cognitive effects, just its possible benefits in multiple sclerosis.
DeleteI have recently started with 0.5mg of clemastine, which is well below the typical allergy dose. Any pro-myelinating effect should take months to become evident.
Anonymous, I use pterostilbene as an alternative. It is a supplement. Ibudilast should be similar with regards to PDE4 inhibition, but also is a PDE3 inhibitor which could make it even more attractive to use.
ReplyDeleteI do see a cognitive effect.
/Ling
This is quite interesting recent review:
ReplyDeleteTherapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature
https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00363/full?fbclid=IwAR3dtz4uHexBecSp11Ce0GsTGzag9_HOBr72NaK9ujf0zjtPriTW63tyjZk
The authors hypothesize that exogenous ketones might be helpful in autism.
Maybe we - the BHB users here - should tell them they are right?