Parkinson’s and Exogenous Ketone Esters

(Ian) #1

Question: Do you think it likely that the consumption of exogenous ketone esters will help to mitigate Parkinson’s symptoms?

There have been a small number of clinical trials on humans that appear to demonstrate the beneficial use of ketosis to ameliorate Parkinson’s symptoms (as listed below if you are interested in more details). In addition, there also seem to be an increasing number of anecdotal reports from PD patients (i.e. n=1), who have experienced some form of relief when they adopted a ketogenic diet (see video by William Curtis linked below).

I have a friend who now requires heavy medication for Parkinson’s but will not try a low carb/keto diet because his wife is convinced it’s a “fad” and it goes against the nutritional guidelines … cue heavy resigned sigh …. I know … there’s no need to tell me …. I have tried.

This has led me to wondering if the consumption of exogenous ketones would be beneficial in the absence of adopting a ketogenic lifestyle. I have managed to purchase ketone ester (KE) from KetoneAid and HVMN and brought them into Canada and am hoping that he will try them to see if they have any impact on his symptoms. However, I was wondering about the following:

  1. How likely is it that the exogenous KE will have any measurable impact?

  2. When would be the best time to try consuming the KE, with the conventional drug regime or after they have worn off?

  3. Will the efficacy of the exogenous KE be dependent on him being fat adapted, i.e. his body may not have the appropriate pathways to make use of this alternative form of fuel and won’t know what to do with it?

If and when we go ahead with this experiment, I will be measuring blood sugar and ketones pre-consumption and every hour after consumption. Any other suggestions?

Thanks for any advice or assistance you can provide.

Ian

Background Information

D- b -Hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s Disease, published March 7, 2000.

“The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration”.

D-b-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease, published 2003.

The infusion of the D-b-hydroxybutyrate (DbHB) in mice provides partial protection against dopamine cell neurodegeneration and motor deficits due to improved mitochondrial respiration and increased ATP output. Historic treatment of epilepsy has shown ketone bodies to be a safe treatment method and because of their greater ability to penetrate the blood brain barrier (compared to glucose, particularly in insulin resistant individuals), DbHB may represent a potential therapy for PD.

Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study, published in 2005

Five (5) patients sustained a hyper-ketogenic diet for 28 days and Unified Parkinson’s Disease Ratings Scale scores improved for all five participants. Unfortunately, the sample size was too small to be significant and there was no blind or placebo control. The low protein content of the diet may also have influenced the effectiveness of the drug regime.

Neuroprotective and disease-modifying effects of the ketogenic diet, published Sept 2006

“There is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects”.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/

Novel ketone diet enhances physical and cognitive performance, published Aug 2016

“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 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

New Zealand (2018) randomized and controlled trial with 44 participants assessed a low‐fat versus ketogenic diet in Parkinson’s disease:

The study concluded that “It is plausible and safe for PD patients to maintain a low‐fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in motor and nonmotor symptoms; however, the ketogenic group showed greater improvements in nonmotor symptoms”.

https://onlinelibrary.wiley.com/doi/full/10.1002/mds.27390

William Curtis:

(Full Metal KETO AF) #2

Wow, I think you need @atomicspacebunny! :cowboy_hat_face:

#3

For this question, I can tell you that the brain uses ketones readily without fat adaptation. In fact, some astrocytes in the brain can make their own limited supply of ketones. How much of the ketones in the blood get through the blood brain barrier is going to determine the level of ketosis needed to provide adequate fuel for brain cells that may have become unable to metabolize glucose. Different people see benefits at different levels of BHB and/or AcAc.

From here: https://www.ncbi.nlm.nih.gov/pubmed/11043913

Bohb_plasma_brain
Bohb_plasma_brain.png985×988 91.9 KB

This study goes into detail about which parts of the brain use ketones the most, if that helps narrow down how it might benefit Parkinson’s? Some of it is based on AcAc instead of BHB, but their theory is that testing one provides similar data as the other.

Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study

https://journals.sagepub.com/doi/10.1177/0271678X16669366

the changes in regional and whole brain CMRa were directly proportional to blood AcAc concentration, and that CMRglc decreased inversely with the increase in CMRa. Quantitative region-by-region analysis showed that a blood AcAc of 1.7 mM would sustain about 17% of total brain energy requirements. Thus, when plasma ketones increase, the healthy adult brain meets its metabolic needs by modulating CMRglc in relation to brain ketone availability and uptake

AcAc_plasma_brain
AcAc_plasma_brain.JPG560×776 65.3 KB

BrainAcAcGluc
BrainAcAcGluc.JPG728×833 125 KB

Also, these studies were done using a ketogenic diet or fasted state, but the glucose levels of a regular diet shouldn’t hinder ketone use by the brain. They don’t compete for access through the BBB. I can’t tell you ow much difference this will make to his condition or if eliminating certain foods might provide additional benefit. [for example, it’s said decreasing or at least stabilizing glucose availability helps with epilepsy]

(Eric - The patient needs to be patient!) #4

The american diabetes association no supports low carb (keto) as a dietary option. It is no longer viewed by them as a fad. https://www.dietdoctor.com/american-diabetes-association-endorses-low-carb-diet-as-option

Let us know how it works out. MCT oil can be used as well and it does not taste bad and is less expensive. However you have to ease into MCT to avoid disaster pants.

(Bacon is a many-splendoured thing) #5

Ketone metabolism and glucose metabolism are separate pathways in brain cells, according to some things I have read, which is one of the reasons that ketones can help with Alzheimer’s disease, which is increasingly being understood as a defect in glucose metabolism in the brain. The ketone pathway can still function properly, even when the glucose pathway is damaged. I’ve read about cases where exogenous ketones helped patients who, for various reasons, could not be put directly on a ketogenic diet.

The effect of ketones on Parkinson’s disease appears to be related to their effect on dopamine regulation in the brain. Apart from that, however, I would expect that exogenous ketones could be as useful with this disease as for Alzheimer’s disease. You’d likely need a fairly high dose, in order to compensate for the lack of endogenous ketone production. I hope you can find a way of helping your friend.

(Ian) #6

Thanks guys. Its encouraging to hear that he does not necessarily need to be fat burner to take advantage of elevated BHB in the blood.

@PaulL; the reason for going with the ester is that it is possible to achieve blood BHB levels as high as 3-5 mmol/dl for a period of 3-4 hours, which I hope to demonstrate with my Keto Mojo. Hopefully this will represent a therapeutic BHB level.

I also plan to try the KE and it will be interesting to see how high my BHB will go, from a baseline which floats between 0.6 to 1.2 mmol/dl.

It is my understanding that athletes can consumed up to 3 x bottles of the KE per day without adverse impacts, but I have yet to confirm this with the suppliers.

(Bunny) #7

Something like that:

I think it has to do with BDNF factors; neurogenesis, neural repair and neuroplasticity in other words you have to keep building new neural networks (ketogenic diet not just exogenous ketones but a deeper mitochondrial state of ketosis) when you have Parkinson’s like your seeing in the videos with William Curtis. The brain using more ketones for fuel than glucose? Parkinson’s Disease comes from the brains inability to make dopamine, ketones may help the brain create new neural connections and newer dopamine creating cells from left over neural stem cells?

image
6F239A4B-8B39-4E8E-882A-265BF9BEE201.jpeg900×600 358 KB
image link

image
8DBBD4EA-DB93-4E70-B8F8-69C67715E976.jpeg900×600 309 KB
image link

References:

[1] Brain-Derived Neurotrophic Factor (BDNF): like NGF, CNTF, GDNF, CDNF, and MANF is a protein that promotes brain growth. BDNF is important for longterm memory and helps grow new neurons from neural stem cells (neurogenesis). R…More

[2] Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats.

[3] THE NEUROPROTECTIVE PROPERTIES OF CALORIE RESTRICTION, THE KETOGENIC DIET, AND KETONE BODIES

[4] BDNF Alzheimer’s – The Fundamental Principle - Dr. David Perlmutter, MD.

[5] Broken Brain: Episode 1 - Dr. Hyman

[6] WSJ: Mad-Cow Disease Provides Insight into Parkinson’s Protein Folding

[7] Pig brain cells implanted into brains of people with Parkinson’s

(BuckRimfire) #8

Can anyone recommend an exogenous ketone product? I was listening yesterday to a recent Keto Woman podcast with Annette Bosworth and it seems to me that I know at least two people who might benefit from using them: an elderly woman with anxiety/depression and a co-worker who suffered a concussion a couple of weeks ago. Neither of them is going to be willing to do a proper keto diet.

#9

I like these.

Capture1
Capture2

#10

Raspberry ketones are not the same thing as the ketones produced by the ketogenc diet.

What I would recommend is the exogenous ketone esters. No specific brand recommendation.

(Ian) #11

Thanks Bunny. I will pass on these references and will keep suggesting that he try a keto diet to help encourage neural repair. Unfortunately I don’t think I will be successful because his wife is very anti-keto.

My hope is that he will feel some form of immediate relief by taking a high dose of exogenous ketones and this will give him the impetuous to try a keto diet and ignore his wife.

(Ian) #12

I cannot personally recommend any specific product. I have purchased ketone esters from the following and will be trying them shortly:

HVMN Ketone Ester:

Ketone Aid:
https://ketoneaid.com/

Please note that the ketone esters are very different from the ketone salts. The salts typically represent a racemic (50:50) mixture of the active and non-active forms of BHB. I believe both of the above ketone esters are 100% of the biologically active forms. It is also my understanding that the quantity of ketone salts that you consume may be limited because of the amount of salt (i.e. the cation) that is present in this type of product. Generally the ketone ester can achieve a higher BHB level in the blood than the salts.

(Eric - The patient needs to be patient!) #13

@Knnn Let us know how you respond.

(Eric - The patient needs to be patient!) #14

Maybe there is some logic here that will work: How can keto be worse than parkinsons. If after 2 months he does not get relief from keto them go back. Seems very odd that a diet would be worse than parkinson’s in someone’s mind.

(BuckRimfire) #15

Yes, it would be one thing if you had mild acne and thought a keto diet might help. Then, if someone really thought the diet was risky, they might have a case, but OH WAIT, DON’T TRY TO SAVE YOUR MOTOR SKILLS, YOU MIGHT GET HIGH CHOLESTEROL!!!

#massive eyeroll

(Ian) #16

My friend and I tried a Ketone ester which contains 25 g of BHB ester (I believe) and these are our blood ketone levels (measured with a Keto Mojo):

image

As you can see from the graph, I was already in a state of ketosis and have been for approximately 12 months. My friend who is suffering from Parkinson’s, has never been in ketosis (except presumably when he was a baby).

He consumed the KE after his conventional medication had worn off, to determine if he could feel any affect. Within approximately 15-20 minutes he noted more mental clarity than he would expect, which lasted for approximately 1 hour. Between 30 and 60 minutes he also noticed brief periods of tingling (almost but not quite pins and needles) in his extremities, which he said was similar to the effect his conventional treatment had.

My friend does not have the conventional Parkinson shakes that is seen in the video by William Curtis, as shown above. He experiences cloudy thinking, lose of feeling, poor temperature regulation (extremities get very cold), stiffness and any movement becomes an effort that has to be consciously thought about. While the elevated blood BHB appeared to provide some relief, it was not as effective as his medication.

I had assumed that I would consume my BHB quicker as I am already fat adapted and my body is ready and very able to use blood ketones. However, I was surprised to see that while we had a somewhat comparable increase in blood ketones (his was 0.2 to 3.4, a net gain of 3.2 mmol/L and mine was 1.1 to 4.0, a net gain of 3.9 mmol/L), his ketone levels fell earlier and far quicker than mine, almost as though there was a higher demand?

Considering that there appeared to be some physiological benefits between 0-1hour after consuming the KE, when his blood ketone levels were the highest, I am left wondering if there is room for improvement, i.e. if continued consumption of more KE over time to keep the BHB above 4 or 5 for a prolonged period of time? For example, an initial dose of 25 g and then 3 further half does of 12.5 g every hour.

Also it may be worth trying to elevated BHB levels in conjunction with his medication, however, this is something that should probably be tried with medical supervision.

Does anyone know if there is a maximum recommended dosage?

Any thoughts would be most appreciated?

PS, it was interesting to note that after 4 hours, when my BHB was still at 2.6, my blood glucose was down from an initial value of 5.1 mmol/L to 3.4 mmol/L, which is quite the Dr.Boz ratio.

(PSackmann) #17

Thank you for posting your results @Knnn. My husband is suffering from short-term memory loss and a lack of clarity lately, but he is resistant to the idea of a keto diet as he loves sugar. I had contemplated picking up some MCT oil or KE for him to try, I see from your results that he’s likely to have to take the KE continuously to get the same effect as being in nutritional ketosis.

#19

I found a study (pdf available) where they are measuring such things in the context of humans. (There are a boatload in rodents but the numbers aren’t always indicative of human reactions.) The typical peak and dip lasts about 3 hours feeding of BHB as ketone ester (141 mg/kg and 282 mg/kg of R-3-hydroxybutyl-R-1,3-hydroxybutyrate) dosed according to bodyweight. The higher dose produced a steeper curve, but duration was about the same.

EsterVsSaltsHuman

Then they looked at how often they needed to feed the ester to achieve specific levels:

BHBester

So, there is a bit of buildup with successive feedings, but there’s still peaks and dips compared to a constant influx with a feeding tube. As mentioned above, the transport across the BBB differs by individual, so it’s important to figure out what plasma level needs to be achieved for the desired results. I have to think the supplements will get expensive and at some point maybe they’ll be more receptive to a dietary intervention.

The other thing you might want try is extending the BHB window using MCT oil, if their gut can handle it. I’ll see if I can find a human study on that. It might give you a less drastic rollercoaster.

Yes, one of the side-effects of exogenous ketones is a corresponding reduction in glucose. If you are using an ester, there will be acetoacetate present in addition to the BHB you can test with the meter. Both of these are used by the brain and compensate for glucose as an energy source. The high level of ketones alter the pancreatic hormones to lower glucose.

#20

Oh good, here’s the effect of MCT oil over an 8 hour period. The study is broken down into the 3 specific fatty acids, C8, C10, C12 by their rate of absorption and BHB increase. Their conclusion is that C8 has the most effect.

Combining MCT and esters might be a good strategy for your friend? The bump in ketones from MCT oil isn’t nearly as high and large doses generally cause the gut to rebel.

AUCs for plasma total ketones were not significantly different
between C8 and C8C10. Compared to C10 given alone, both
C8 and C8C10 increased the AUCs for plasma AcAc by 2 fold,
plasma b-HB by 5 fold and total ketones by 2.5 fold

MCToilBHB

P.S.
The C8 oil Brain Octane is more expensive than regular MCT oil, but may/may not give you a bigger boost at a tolerable ingestion level.

(Bacon is a many-splendoured thing) #21

That certainly sounds reasonable.

The one caveat I would put forward is that there is no research, so far as I know, to demonstrate what happens when exogenous ketones are consumed in a state of high insulin. Harm doesn’t seem likely, but I don’t believe we know for sure. @carolT? Anything you might add? I’m not spotting anything on PubMed.

Though your friend’s experience demonstrates that they do get into the brain, at least.