Who lives in Libya? And Raising the level of BHB in your blood.

Today’s post is mainly about some “home-research” that was sent to me by a company that sold me C8 oil (caprylic acid MCT oil).

It is not peer-reviewed research, but it is a well thought out home experiment measuring the level of the ketone BHB in the blood of two healthy young adults testing a range of commercially available products. It is important to note that BHB was measured in blood and not urine, which is a big plus for the experiment.

Dr D’Agostino’s starting dose

First, a recap of where we started a few months ago in this blog.

One of the leading ketone researchers is Dr D’Agostino and his suggested starting dose on ketone supplements is 10 ml of Ketoforce and 10ml of C8/caprylic acid.

We saw in earlier posts that the amount of BHB produced by taking C8 is highly dependent on whether it is taken with food. Taken on an empty stomach resulted in more BHB in the bloodstream.

10 ml of KetoForce contains 4g of BHB along with 500mg of sodium and 500mg of potassium.

BHB salts and BHB esters

Until recently BHB supplements were all salts, so the BHB was combined with sodium, potassium, calcium or magnesium.

Taking large amounts of sodium, calcium, potassium or magnesium will likely disturb the electrolytes in your body and may cause you problems.

Ketone esters are composed of a ketone molecule like BHB bound to a ketone precursor using an ester bond (butanediol or glycerol).

Ketone esters are commercially available, but very expensive.  They are currently used by athletes and the US military.

The first commercial product was developed based on the work of researchers at Oxford University in the UK, but the resulting product cannot legally be sold in the UK. HVMN, a company in the US, are currently selling it as a supplement for athletes. I wonder if it has been declared a banned substance by sports doping agencies.

Some of the research:-

Novel ketone diet enhances physical and cognitive performance.

Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson’s disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [³¹P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.

https://hvmn.com/blog/exogenous-ketones/beta-hydroxybutyrate-or-bhb-all-you-need-to-know#Murray2016

The Military as Early Adopters

For centuries military forces have sought to gain a competitive advantage using drugs, so it is not surprising that the current US military are interested in ways to increase physical endurance.

Survival rations for downed airmen, or just reducing the weight of food rations for Special Forces, would be obvious applications for BHB esters.

In modern times it was the Germans who made the greatest military use of drugs with their Pervitin tablets that enabled their soldiers and airmen to fight for days without sleep. Pervitin turned out to be Methamphetamine. Such drugs are used today by irregular forces.

Extensive use was made of drugs to counter altitude sickness in Afghanistan, first by the Russians and later by the Americans. Diamox/Acetazolamide is the Western drug and this same drug has application in some channelopathies and some types of autism.

Drugs that improve exercise endurance, and so are likely banned for use in sport, are potentially interesting for people with mitochondrial disease, vascular abnormalities and even glucose transporter dysfunctions. In short if you have restricted ATP production in your brain, anything that can overcome whatever the route problem is, should improve brain function. Alzheimer’s disease is a good example where apparently quite different reasons result in reduced power output within the brain. 

I thought it was encouraging to see that military funding is being used to develop medical therapies for PTSD and suicide prevention. The latter was the application for the hormone TRH, which I suggested as a possible autism treatment, since it affects a chain reaction of important hormones affecting mood.

The n=2 home trials of BHB-raising supplements

You can read the full report by clicking the link below

https://ketosource.co/keto-experiment-exogenous-ketones/?utm_source=drip&utm_medium=email&utm_campaign=Keto+Update%3A+Results+from%C2%A0Ketone+Supplement+Experiments+AND+Metabolic+Health+Summit+Interviews#disqus_thread

I have extracted some interesting highlights.

·      HVMN and KE4 are very expensive ketone esters (red and green lines)

·      C8 MCT oil is the product that I currently use (20ml a day) (purple line)

·      Keto Max and KETOCANA are ketone salts (blue and orange lines)

 Recall an earlier graphic of "the ketone zone" so you can put BHB levels into context.

Summary: The Takeaways

·       We confirmed that ketone supplements increase ketones: All of the ketone supplements tested resulted in an increase in ketones for a temporary time period.

·       Rapid 3-Hour Windows: Ketone esters and ketone salts rapidly increase ketones within 30 minutes. The effects last for a ~3 hour period.

·       Slow 5-Hour Window: C8 MCT oil increases ketones more slowly. However, the ketone increase lasts for a more prolonged period of ~5 hours (see C8 MCT Oil research review covering this).

·       What Does this Say About When to Use Which Supplement? This is a complex question that requires further investigation into the different applications. However, we have three hypotheses to start with based on these results.

1.     For higher ketone boosting needs: If you are looking to boost ketones into the therapeutic range of 2-4mmol, it is more cost effective to take KetoCaNa (Ketone Salts). But a more gut tolerable option would be a Ketone Ester – at a greater price. Both are able to boost ketones enough to meet this target.

2.     For lower ketone boosting needs: If you are looking for less than a 1 mmol boost in ketones, the most cost effective and convenient (longer duration) approach is via C8 MCT oil. This may be most relevant to A) People not on ketogenic diets who want some of the ‘satiation benefits’ of ketosis, and B) People on ketogenic diets who already have raised ketones and only want a small additional boost (e.g. you’re at 1 or 2 mmol, and want to increase to 2 or 3 mmol respectively).

3.     For the highest ketone boosting needs: Should you want a greater increase in ketones for any reason Ketone Esters are the best option (this article explores where and why this may be interesting)

My conclusions

The effect of C8 is slightly different to Ketone salts like Ketoforce and I think D’Agostino’s advice to combine them is wise.

A dose of 20ml of C8 appears a good upper limit, since its effect at producing BHB gradually fades. Better to make sure it is taken without food to maximize the effect. Even though it is the cheapest supplement there appears to be no point taking larger doses like 50ml.
Ketone salts are definitely limited by their composition of sodium, potassium, calcium or magnesium. I think high doses are extremely unwise. D’Agostino’s 10 ml of Ketoforce seems safe.

Ketone esters are very expensive, but do actually provide a genuine energy-boosting level of BHB, which will also trigger all the other suggested effects of BHB (summarized in the old post below), quite possible at increased levels.

Ketone Therapy in Autism (Summary of Parts 1-6)

So I suppose the ideal autism research study would be to use KetoneAid KE4 or the HVMN BHB Ester, as used by the US military.

I expect the BHB Ester would have a big effect on someone with Alzheimer’s disease. They have a problem with the glucose transporter at the blood brain barrier and with reduced insulin sensitivity. The large amount of BHB from the ester supplement would provide an alternative fuel for the mitochondria, which are not producing enough ATP from glucose to power the brain.

We saw that Nestle is investing in MCT as a nutraceutical for Alzheimer’s. Today’s home research suggests that high doses of MCT are not going to be effective at raising BHB levels in the blood to a very significant level. BHB esters look much more promising.

This would be an expensive Alzheimer’s therapy, but still much cheaper than relocating to a care home. 

I did check and there actually is a case history; it is a physician wife treating her own husband who has early onset Alzheimer's. She read the research and translated it into a novel therapy for him. Nice work! This would of course be frowned upon in most countries as treating hubby like a guinea pig and doctors are not meant to treat family members, but to me it looks like the most caring thing she could do.  The good thing is that she published the result. Mainstream doctors treating their own children with autism, or even sometimes others, rarely seek to publish/share their results, so helping to maintain the convenient false perception that all autism treatments are just quackery (some are, while some clearly are not).

A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s

• After six to eight weeks of taking 28.7g of the KME thrice daily, he began to exhibit improvement in memory retrieval, spontaneously discussing events that occurred up to a week earlier. He was again able to perform more complex tasks, such as vacuuming, washing dishes by hand, and yard work.

• Plasma βHB levels were measured occasionally to assess KME-plasma βHB dose-response relationships (Fig. 2). Noticeable improvements in performance (conversation, interaction) were observed at higher, post-dose βHB levels, compared to pre-dose values.

• In treatment of TP’s long-standing AD dementia, KME-produced repeated diurnal elevations of circulating βHB levels were clearly effective, during the 20-month study, in improving behavior, and cognitive and daily-activity performance. The physician-caregiver noted that performance seemed to track plasma ketone concentrations, with conversation and interaction declining as levels fell toward baseline. From requiring almost constant supervision, TP became much more self-sufficient on KME

The question in autism is what level of BHB do you need to maximize the effect and how long does this spike in blood BHB produce its beneficial effect. Do you need a constant level for 24 hours (I think not)? Do you need one BHB elevation/spike a day? Does a second daily dose have any benefit?
The BHB ester would be a good research tool, since it should not disturb electrolyte levels.

Who does live in Libya?

Anecdotal evidence has always got to be taken with a large pinch of salt, but if all you are doing is an N=1 trial that is often all you have got.

From more than half a year of experimenting with the combination BHB salts and C8 oil, the effect is clear. It causes an increase in relevant speech, directly related to current activities. You could call this unprompted commenting.

Monty will now answer the phone at home, rather than just hanging up to stop the annoying ringing noise, or having an ultra-trivial conversation. He will have a functional conversation in either of his two languages. This was particularly noted by his Grandmother as an improvement.

The good thing is the increased conversation fades when BHB/C8 is paused and returns when re-started.

Along the way we have discovered that not all BHB salts are equal. The Ketoforce liquid is the best, because it has most effect and does not disturb electrolytes, as Primaforce BHB powder appeared to, not by much, but enough to have an impact.

Using a mixture of C8 + C10 oil, produced a negative effect (aggression) after a few weeks. So while C10 may have a unique effect on mitochondria, beneficial to some, it was not tolerated.

10ml of Ketoforce and 20ml of C8 a day means one bottle of Ketoforce and one litre of C8 lasts 50 days.

The beneficial effect is not on the magnitude of bumetanide. The Ketoforce/C8 therapy costs 15 times more than bumetanide, but I think that really just means that generic bumetanide is extremely cheap.

Adding the small 0.5mg dose of Clemastine in the evening does seem to have an incremental effect after a few weeks.

It does appear to manifest itself again in improved speech. Now the comments are not related to current activities, but also past events and making connections.

“Colin has a moustache, like Poirot”

Colin is a friend of mine who Monty last saw a few months ago. He does have a moustache and so does Hercule Poirot.

The strangest recent “conversation” started with:-

“Who lives in Libya?  …  Do Indians live in Libya?” asked Monty

“No, Indians do not live in Libya, Arabs live in Libya”, I replied.

“Indians live in London” he countered

            “Yes, some Indians do live in London, but a lot more live in India”

“Who lives in Israel?” he asked    (We did recently visit Jerusalem)

            “Jewish people and Arabs live in Israel”, I replied

            “Who lives in France?” I asked

“Leopoldine” (a former classmate from school) he answered

            “Who lives in Italy?” and so it continued.

This is not the sort of “conversation” you normally have with Monty. This was the longest ever "conversation".

You would not expect him to recall that London has a large population of Asian descent. He lives far away.

Is this the cumulative effect of BHB/C8, or an emerging benefit of a quarter dose of an OTC hay fever drug?

Clemastine, taken in the evening, has had no negative side effects and is not expensive. $10 buys 60 pills that will last 4 months. Daniel Kerlinsky, the enlightened US psychiatrist we encountered in a post a while back, was keen to point out that it takes months for low dose Clemastine to show its effect (myelin, microglia or both).

In our case BHB/C8 looks like it is heading towards being included in the PolyPill. The only side effect is feeling thirsty, which is manageable. I am surprised to be considering adding what is a Californian diet therapy to my son’s autism therapy. Incidentally he has not lost any weight, he continues to gain it.

The jury is still out on Clemastine. Due to the onset of its potential benefit being very slow, it is not so easy to make a withdrawal trial (stopping a therapy, seeing if the believed effect is lost and then restarting to see if that effect returns). I will wait to see the feedback of other readers of this blog.