My Beta-Hydroxybutyrate experiment: increased activity tolerance and reduced PEM

[enduin]

I have recently been experimenting with beta-hydroxybutyric acid supplements (commonly known as ketone salts) and I wanted to share the results.

I know that a lot of people have experimented with low-carb diets (although I’m not sure how many experimented with a proper ketogenic diet which is low carb, moderate protein and very high fat) and while a few have had some improvements, the majority don’t seem to gain anything from it, with some people even getting worse. I, myself, have experimented with a low carb (but not strictly ketogenic) diet years ago to no avail.

The reason why I got interested in ketone salts is that with the glycolysis cycle, the final step before the entrance in the mitochondria is pyruvate, but we can’t supplement pyruvate directly. On the other hand, with the ketogenesis cycle the final step is a ketone body, like beta-hydroxybutyric acid, which we can ingest as an oral supplement. This is obviously an oversimplification, but it’s just to give an idea of the reason for my interest in this.

Knowing that there are probably roadblocks somewhere in our energy creation cycles, I was curious to see what would happen if instead of relying on my body to produce ketones (which I have a feeling is something it doesn’t do very well), I could provide it with the final product ready to go. Also worth mentioning is that ketone bodies can cross the blood brain barrier and can be utilized directly by the brain.

So, I bought some ketone salts. I chose the Nutricost brand because it’s just pure beta-hydroxybutyrate salts (Ca, Mg, K, Na salts). Another possible option is Perfect Keto, which is flavored. I would avoid all the other stuff, especially generic “raspberry ketones”. Now, I will warn you, these ketone salts are NASTY! It’s kind of like consuming solvents, so if you are taste-sensitive, maybe the Perfect Keto version is a better option for you. I, on the other hand, would rather suffer the horrible taste but not ingest any unnecessary “natural flavors”.


So here are the results:

The first day, on empty stomach, I took 16g of Ketone salts. Within 30 min I started feeling a noticeable stimulation and energy, which lasted 2-3 hours and slowly faded. But, I also got a pretty strong attack of diarrhea. These ketones can be quite upsetting to the GI tract so that’s something to keep in mind if you are prone to GI upset.

The next day, I tried taking 8g, still on empty stomach, and noticed that the increase in energy was much milder, bordering on placebo, but I got no diarrhea. Most importantly, when I tried doing some light activity I noticed I was not getting as tired as usual.

Next, I tried taking the Ketones on full stomach, and noticed that there was no effect.

Next, I tried multiple dosing, with an initial 8g dose on empty stomach in the morning, and subsequent 5g and 4g boosters around noon and 4pm. I skipped breakfast and had a lunch that was mostly fat with some protein, and zero carbs. This experiment was the most successful, as I then proceeded to intentionally overdo with an amount of activity that would 100% result in PEM and didn’t experience PEM or a crash!

Next, I experimented with eating a Keto diet for 4 days while taking the Ketone salts in the morning. I wanted to see if maybe the Ketones would jumpstart something, but they didn’t. My energy levels were improved after taking the Ketone salts and would decrease after a few hours, which told me that the diet was not doing anything. Urine ketone testing was inconclusive as to whether my body started producing ketones or not and if yes, how much. The bottom line was that the effect that I was getting was solely from the Ketone salts.

Lastly, I experimented with taking a dose of Ketone salts in the afternoon after getting a mild-medium exhaustion crash. One of the symptoms I consistently experience (along with nausea, headaches, etc) is a feeling of my arms being dead weights. After 30-40 min from the ingestion of Ketone salts I started feeling better and the “dead weight” feeling in my arms almost entirely disappeared. When I say “feeling better” I don’t mean feeling like I could do more stuff, just feeling more like normal tired instead of crashing tired.

So, what did I learn? It seems like Ketone salts can be useful in gaining some extra energy in high doses, but that is at the expense of pretty bad diarrhea. The most useful application, on the other hand, seems to be as something to take on days when I know I have stuff to do that has a very good chance of making me crash if I’m not careful. In this situation, coupled with skipping breakfast and a medium-protein/high-fat/no-carb lunch, and with boosters as needed, it seems to be useful in warding off PEM and crashes.

Besides the diarrhea from the initial high dosage, side effects have been fairly minimal: some excessive urination (so hydration and proper electrolyte intake is important) and headache was all I experienced. However, between this and the issue with meals, it’s not something that I would do every day.

My wife, @Basilico offered herself as test subject number 2. Unfortunately, she did not experience any improvement in energy, and taking Ketone salts during a mild crash did nothing to ameliorate the symptoms. She is definitely a non-responder. I have a hunch, based on the results of the Naviaux study and the differences between male and female CFS patients, that this is not a coincidence, and I have a feeling that these Ketone salts supplements might be more useful for male CFSers rather female. If you decide to experiment yourself, please post the results!

 

[Basilico]

This is a reminder to explain how Ketones affect your blood glucose/insulin sensitivity, and what people should monitor if they decide to try this experiment themselves.

Also, can you mention the results of taking the Ketone salts without a keto diet (normal/high carbs)?

 

[serusaert]

@enduin - this is really interesting stuff - i have avoided ketone salts as they really do taste quite awful as you have warned - i really wish it was not so nasty tasting.

taste aside, i will experiment with it again as i am taking a break from keto for summer fruits, and, @Basilico - i will report back on how it goes for me (and i'm not currently in ketosis).

i have also found an interesting thing: when i come out of keto, i experience a bit of a boost energy-wise for 3-5 days and i wonder if it's due to having two fueling systems going at once - perhaps providing fuel/substrates that we don't normally have during a short overlap period.

the fact that the boost does not last long seems to reinforce the notion that our bodies really do want to function as either carb-burning or fat-burning but not both. also, i would add that once the 3-5 days of energy are over, symptoms return and they can get worse than when i am in ketosis. for me, ketosis seems to mellow out the neurological/neuropathic aspects of CFS/ME. it also helps me control SIBO as i tend to have much fewer cravings for foods that make me sick when i am in ketosis.

 

[enduin]

Ok so this is a little addendum to the initial post:

- it seems like taking ketone salts does something to my glucose sensitivity. I'm pre-diabetic, although after 4 years of careful monitoring my carb intake, I'm not sure I would still qualify as my glucose tolerance has improved. Unless I don't sleep, in which case the following day my glucose tends to spike more than usual. Anyway, taking ketone salts seems to overall LOWER my blood glucose if I'm either fasting or eating keto, but then it causes my glucose to spike HIGHER when I eventually eat a normal carb meal. Could be a rebound effect, not sure. Just something to keep in mind if you, like me, have pre-diabetes and experience symptoms from glucose fluctuations. The best approach for me seems to be to take the ketone salts in the morning on empty stomach, skip breakfast, have a keto lunch with oen or two more ketone doses, and then have a normal dinner with a 20 min walk (if I can tolerate it) right after to lower the blood glucose.

- also, carbs BEFORE taking the ketone salts seem to neutralize the effect of the ketones, so the order mentioned above seems to be important to obtain results (ketones on empty stomach, with some redoses, keto lunch and no carbs until dinner).

@serusaert it would make sense that you have fewer neurological symptoms while in keto, because ketones can cross the blood brain barrier, and they do exert an anti-inflammatory effect. Let us know if you experiment with the ketone salts and what results you get. If you really can't stomach them you can put the powder in gelcaps. It's a pain but it helps, right @Basilico ?

 

[Basilico]

i have avoided ketone salts as they really do taste quite awful as you have warned - i really wish it was not so nasty tasting.

I can't tolerate the taste at all - I start dry heaving before I can even start taking it! @enduin put a full dose into a lot of gelatin capsules, which was a pretty big pain since the ketone salts seem to be pretty hygroscopic, so by the end the powder was getting very clumpy and hard to encapsulate. However, it can be done, and in that form I can take it with no problem.

Unfortunately, the Ketone salts really have no effect on me. I seem to do a little better eating carbs, so perhaps my ketone pathway works even worse than my glycolysis pathway. Interestingly, I often feel better after eating, while @enduin tends to feel worse. I'm not sure if that is relevant to how we respond to the Ketone salts, but perhaps it plays a role.

i have also found an interesting thing: when i come out of keto, i experience a bit of a boost energy-wise for 3-5 days and i wonder if it's due to having two fueling systems going at once - perhaps providing fuel/substrates that we don't normally have during a short overlap period.

This is interesting. I don't think that @enduin has any sustained effects after the day that he takes the ketone salts. Perhaps this is because your body is actually producing ketones endogenously while his body does not.

 

[paolo]

If you do the math, a dose of 10 g of BHB gives about one kg of ATP. But a human being consumes about 70 kg of ATP per day. I am not sure, but the amount of energy from a dose of 10 g of BHB seems pretty small.

 

[enduin]

It certainly is small, in the grand scheme of things. It's obvious that we can't rely on ketone salts for the entirety of our body's energy demand. However, the ketone salts might be able to temporarily relieve some of the energy starvation from crucial areas, such as the brain, since ketones can cross the BBB. This would be my guess.

 

[paolo]

I have been taking 10 g of BHB at breakfast for 6 days. I feel some improvements, but I am not sure. We'll see. @enduin Any update with your own experience?

 

[enduin]

Can you please elaborate on how you are taking it (empty stomach then wait some time before having any food like I was doing or something different) and what are the improvements you are noticing?

Because of the annoying headaches I get and the issue of foods and meals restrictions, I'm only using the BHB as needed when I know I have to do something that would give me PEM.

 

[Alvin2]

If you do the math, a dose of 10 g of BHB gives about one kg of ATP. But a human being consumes about 70 kg of ATP per day. I am not sure, but the amount of energy from a dose of 10 g of BHB seems pretty small.

Thats not bad, i have no idea how much an ME/CFS patient produces but adding 1/70th the energy of a normal person would be a huge improvement for many of us. Take a few more grams and keep adding energy.
That said i know nothing about this chemical, is it safe to take, are there side effects, will tolerance develop, is it toxic, i dunno.

 

[enduin]

Yes it is safe to take and no it's not toxic, it's produced naturally by the body when carbohydrates are not available as a source of energy. There might still be mild side effects, for example I seem to get headaches with it. The main problem with just taking more to possibly have more energy is that, taken orally, BHB can easily upset the GI system and lead to diarrhea. If you read my first post I explain the dosages I used and what the threshold was for me.

The oral route of intake is the main limitation. I have no idea if BHB can be used intravenously, and couldn't find any mention of this online, but if it were, maybe a slow IV drip of BHB and saline could be an interesting as a way to provide a more significant amount of energy via ketones.

 

[Wishful]

Just to confuse matters, I found that increasing my insulin level (by eating carbs) increased my symptom severity by increasing tryptophan transport into my brain, an effect that was blocked in I took branched-chain amino acids with the carbs. So, if the BHB is dropping you insulin levels, it might be reducing TRP levels in your brain, reducing your symptoms, rather than by boosting ATP. You could probably test that by seeing if high carb intake (for some reason starch seemed more effective for me than sugars) increased your symptom severity, and whether BCAA's block it. For me the severity climbed rapidly about 20 minutes after ingesting the starch, then decreased more gradually.

I tried a keto diet: it just made my muscle aches significantly worse.

 

[Binkie4]

I bought some perfect keto on the advice of my Consultant early in July, took a small dose once a day for a week and stopped because I felt worse.
Have just started again, small dose twice a day for last two days. I find it ( peaches and cream) palatable when dissolved in orange juice. So far so good; slight improvement in energy even on day 1.
Obviously will continue. I am taking a much lower dose than advised on packaging. It is expensive and Consultant recommended a lower dose.
Always hard to know what is a cause and effect.

I have not tried a keto diet.

 

[enduin]

Just to confuse matters, I found that increasing my insulin level (by eating carbs) increased my symptom severity by increasing tryptophan transport into my brain, an effect that was blocked in I took branched-chain amino acids with the carbs. So, if the BHB is dropping you insulin levels, it might be reducing TRP levels in your brain, reducing your symptoms, rather than by boosting ATP. You could probably test that by seeing if high carb intake (for some reason starch seemed more effective for me than sugars) increased your symptom severity, and whether BCAA's block it. For me the severity climbed rapidly about 20 minutes after ingesting the starch, then decreased more gradually.

I tried a keto diet: it just made my muscle aches significantly worse.

What makes you think that it's the tryptophan that it's the problem and not the insulin itself? Just curious. I quickly took a look at the studies on the effect of insulin on tryptophan transportation and there doesn't seem to be a general consensus on the effect with some studies suggesting even that it's not very significant (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1275568/)

As far as the ketones, there are a lot of possible explanations and a chain reaction that results in less tryptophan being transported in the brain could be one of them. Let's not forget that ketones are also anti-inflammatory so that's another possible route of action. However, seeing how the effects seem to be dose dependent and not last very long, I'm tempted to use Occam's razor and assume that it's because they provide some extra energy to energy-starved cells.

A keto diet I think is a waste of time for most of us. If you ever feel like giving it a second chance, supplementing with BHB as per the description in the first post directly would be my suggestion.

 

[Wishful]

It's definitely the TRP, since taking a tablet of that greatly increased my symptoms, which was totally unexpected. I had read that insulin increased TRP transport into the brain, so I tried BCAA's to see if they had an effect. They blocked it quite effectively: I could eat a TRP-rich meal, such as chicken, without triggering the symptom increase that would happen without the BCAA's. Insulin was my guess for why my symptoms increased 20 minutes after ingestion of plain cornstarch; it seemed a plausible time frame for that to happen. The link you posted does make it sound like a minor effect, but maybe ME/CFS is sensitive to minor effects. I didn't come up with any better explanations for the TRP/BCAA response.

I'm a bit skeptical about ketone's effect arising from anti-inflammatory activity. I haven't found any beneficial responses from a variety of anti-inflammatorys. I have had strong negative reactions from herbs that are said to 'strengthen the immune system'. I think my baseline level of symptoms arise from normal levels of cytokines, so reducing them doesn't help, but I'm sensitive to increases in them.

Using BHB for a trial of a keto diet sounds like a good idea, but I'm just not convinced that the reduced ATP levels is a major component of ME/CFS's feedback loop, but rather that it's a side-effect. I think it's more likely an incorrect response to the immune system's normal function.

I had a thought about this issue last night. I wonder if normal people suffer from the reduced pyruvate/ATP from t-cell activation, but either it's at a lower level or there's a properly-functioning mechanism that overrides it. Maybe Dr. Davis's group could try the serum of a non-ME/CFS patient who is suffering from t-cell activation, to see if if the ME/CFS cells regain normal function or not. I've passed that suggestion on to the OMF. It seems like a trivial test, with potentially interesting results.

 

[serusaert]

@enduin - i have to say thank you for helping me understand that ketone salts do not taste the same as ketone esters (i.e., the ketoforce product). they are, in truth, quite passable for me. i can down half a scoop in a small glass of water - no problem. and i have discovered that my usual fatted coffee tastes just fine with half a scoop of the ketone salts. it seems to elevate my blood ketones for a fair bit of time. i think it helped me avoid the keto flu this time around.

when i take it in the am with coffee, it's blended with 2 tbsp C8, 1g D-ribose, 1g inositol, 1 tbsp pork leaf lard, and 1 g glucose (to cut the coffee bitterness - it goes a long ways once my palate shifts to keto).

i find that this combo, plus a cap of Magnesium Threonate, helps me focus and work. i feel fewer jangs and clangs, and even tho my blood glucose goes way down to 80 - 90, my ketones are way up around 2.5 - 3.0. normally, my ketones are between .5 and 1.5.

i took it as a PEM remedy along with arginine and citruline and found it to help. i think i will be taking it only in AM and PM (with the LDN).

as to why keto helps some and not others, i suspect that for me, it's due to SIBO and the damage it's caused to my short intestine. i would suspect that if not for these issues, i would not find it improves my symptoms. i do think that the neuro-calming effect of keto helps me a lot.

 

[enduin]

You are welcome. Have you ever tried to take the ketone salts on their own first thing in the morning?

Btw, I would be very careful taking ketone salts with D-ribose. It's known that D-ribose should not be taken with hypoglycemia and ketone salts cause the blood glucose to drop. I remember reading somewhere of someone who got hurt using D-ribose while in hypoglycemia.