Keto MAX Scam or Supplement? A look at the research

 

R-BHB Scam or Supplement? A look at the research.

Use Of Supplemental Beta-Hydroxybutyrate (BHB, R-BHB) in humans has exploded in the last 2 years. With it has come reports of many miracles and the associated skepticism and push-back.

Does the research justify the excitement and the predictions that this will be the biggest and most important supplement to come to market?

The avalanche of people reporting increased wellbeing when consuming R-BHB, KetoMAX will continue. What has the science said? What will it say in the years to come?

NASA, Oxford University and the US Military have been key investigators of exogenous ketones.

Is there a mechanism in the research that supports the anecdotal evidence?

Goals for this blog are:

  1. To establish beyond doubt that humans should not be defamed, harassed, ridiculed or intellectually bashed for using and promoting ketones by demonstrating its proven and theoretical uses.

  2. To establish that we are putting R-BHB Pure therapeutic ketones into our blood and the blood of our customers.

  3. To demonstrate the research that R-BHB in the blood is safe and very likely life-enhancing.

  4. To explore the many applications for ketones that the world of science is rapidly exploring. (40 of the studies here are from 2017 or 2018)

  5. To explore why KetoMax is so loved/hated as/despite being the only daily use R-BHB supplement on the market.

  6. To introduce readers and fitness experts to some of the researchers who are investing their lives in better understanding the role of exogenous ketones in the 21st century.

* The goal is not for you to buy ketones.

* The goal is for people to understand enough to let those who choose take and distribute ketones do so in peace.


MY MANE IS KEEGAN SMITH - THIS IS MY KETONE STORY

If you've not questioned my character or the character of whoever introduced you to ketones then skip ahead to the science. If you have then it might be valuable for you to consider the human side of this equation.

This article took about 60 hours to research, compile and edit. I wrote it because I care (12,300+ words). Research doesn’t change lives, application of research does. If you’re not drinking KetoMAX you’re not getting the benefits. Real results are what interest me more than debating over research. In the face of diabetes, obesity and mental disease epidemics it doesn't make sense to me that people are violently opposing something the research world and top scientists are very excited about. I have a coaches mentality, I've been coaching since my earliest memories. Coaches look for best practice and opportunity to do something that others will be doing 5-10 years from now.

I was able to play a role with the Sydney Roosters NRL title in 2013 (as Head of Strength, Speed & Nutrition). We won against the odds. I've also helped many athletes, coaches and average Joes achieve beyond their expectations over the years. My desire to innovate and move ahead of the pack also allowed me the honour of hosting Sonny Bill Williams for a 10 day 1-1 camp at my house in 2017.

I understand not everyone agrees with this approach of early adoption and experimenting to find an edge. It’s worked for me. It’s how I live. I don’t mind standing apart from average, in fact, I can’t stand being average.

The research below suggests the potential for Beta-Hydroxybutyrate to give its consumers an edge. The many therapeutic applications of R-BHB being explored justify the use and distribution of this technology (unknown to 99% of society).

Another similar intervention that I have tried, and believe in, without “scientific backing” is the carnivore diet for those with auto-immune issues. Is the science anywhere near where it is for BHB?... absolutely not. Are there thousands of people screaming from the rooftops that it has transformed their lives?... absolutely.

To ignore the experiences of individual people is hard to justify since that is the end goal of all the research, to help individuals.


Beyond the BHB research, like with carnivore diet, my experience is that many people feel better on KetoMAX. These people often keep researching, make other changes, and remain enriched humans for life, regardless of how long they stay on KetoMAX.

While many elite athletes and bodybuilders love ketones, the biggest application I have seen is for those who’ve “tried everything” and failed. Those who don’t have the energy to get to the gym. I know how this feels after having chronic fatigue myself. To many people, this simple great tasting powder, a 20-second daily intervention, has been life-changing. Below I'll share what the science says is happening for these people.


FULL DISCLOSURE

There are many people who've stated that they think I’m lying or scamming.

When I started with this Pruvit I had a solid 6-figure education business and was living all my dreams with RealMOVEMENT Project. I already had the time, money and geographical freedom I left the NRL for. I was serving coaches and helping them live their dreams.

Life was good.

I wasn’t looking for another job. I was busy.

I didn’t believe in the network marketing model. Even still I liked the ketones, I shared the ketones to test them more widely, good research involves increasing the sample size. Other people liked the ketones and it became a massive business almost overnight. Surprisingly my Pruvit business passed RealMVMT in terms of both INCOME and probably IMPACT.

My mission is to improve the human experience.

Starting with myself, expanding out as far as I can reach.

In my 20's I explored over 40 countries, learned 2 other languages and read a lot. On my travels I saw massively wasted human potential. Violent societies, wasted labour, neglected children with little hope or opportunity, many things I could not accept.

I was 100% sure during that exploration that men, women, and children are living to a fraction of their potential. I made it my mission to change that. This may sound cliché or ego-driven, regardless, it is the truth.

I’ve worked in orphanages and taught English to poor kids, I’ve been a youth worker in the desert of outback Australia, I’ve written hundreds of blogs and way too many thousands of twitter, facebook and instagram posts in an attempt to show people they can live better.

In 2014 I created RealMVMT Project together with 2 friends. RMP is a vision for the next evolution of “fitness & self-development.” Human potentiation excites me. Culture is certainly shifting rapidly in this direction and RMP has changed a lot of lives.

 

I discovered exogenous ketones in 2016 I was excited.

I learned about them from a cancer researcher who happened to be massive and shredded, Dr Dom D’Agostino. I love experimenting with things that make life better. I wanted to try exogenous ketones.

At the time I had a lingering fungal infection and seasonal allergies that were getting in the way of my mission. I needed to make a change. The science looked and sounded good. I tried to get the ketones from Pruvit but they wouldn’t ship to Australia.

I did the ketogenic diet instead. I had some improvements but it wasn’t a smooth transition. Eventually, a friend reached out and said “what do you know about ketones and ketosis.” I ordered the ketones. I felt amazing. I shared them with a few coaches I worked with. The feedback was positive.

Turns out I was one of the first people in Australia to publically advocate, to a decent size audience, about Exogenous Ketones. It was a risk in 2016. There were fewer papers and the general public knew very little about BHB. The ketogenic diet was a lot more obscure than it is now.

The research was clear on safety and it was clear that they did in-fact raise blood ketone levels. Joe Rogan and Tim Ferris, big names who’s brands run purely on the honesty of their opinions were telling the world about them and Charles Poliquin and Joe DeFranco were making them available to their audiences. I took the leap.

Having risked my life in war zones in Mexico and Colombia (not an exaggeration), I wasn’t overly scared about the consequences of being wrong here. I also trusted that people would tell me if they didn't like them.

I’ve since made a lot of money. More than most people make in many years or decades of work. It was a small side-project that I didn’t expect a financial return from. I didn’t expect it but I’m glad it happened.

It turns out people love ketones.

Over the last 4 years over 100,000,000 serves of ketones have gone out from Pruvit.

Could a product have gone viral just because of network marketing or does market popularity in itself give clues that something important might be happening?

If the first million serves caused NO or negative impact, at around $10 aud a serve, would the other hundred million have gone out?

Maybe there could be a third factor involved.


THE TIM FERRIS + JOE ROGAN FACTOR (links below)

In the age of TV, The masses have been treated like fools. Long-form podcasts are a social revolution that has ended the era of TV (still squirming but basically dead). The new era of hyper-connectivity is about real people getting real results.

Social media has exploded.  People are now learning from other people experiences on a rapid global scale. Anyone who has done something special can now tell their story and express their character to millions, maybe hundreds of millions of people in long unscripted, unedited format.

The world will never be the same again.

Dr Dom D’Agostino has become the world leader on ketosis and exogenous ketones via these forums. Keto diet has been advocated by both Ferris and Rogan they also have both publically endorsed Pruvit products (Rogan switched brands to L-R GoBHB after the MLM backlash hit). The result is a global explosion of people exploring alternatives to the “death in moderation” prescription or the “SAD - Standard Aus/American Diet.”

Has KetoMAX impacted the health status quo? Will we see an end to obesity, diabetes, mental illness and cardiovascular disease in this lifetime? It’s hard to say. What I can be 1000% sure of is that Pruvit has fuelled a powerful conversation that the world needs to have.

What are ketones?

How Many Carbs Should I Be Eating?

What is the impact of lowering/eliminating carbs?

There are now tens of thousands more doctors and dietitians who finally know that ketosis is not synonymous with keto-acidosis.

I have great hope for the world. This is one song that reflects that hope.

 
 

Humanity is eating itself to an early death through “food as entertainment.”

We may also be eating ourselves to stupidity and misery, worse than death.

 
 

Upon the explosion of interest and results, people stepped forward to be the authority and say this is a scam. It must be, it’s MLM.

Most of them had done no research and still haven’t.

Those who have done some research have focussed on fat loss and performance enhancement.

One aspect of the metabolic upgrade being explored with BHB.

Ph.D. scientist Brianna Stubbs (the link is a great review of the research), an international level Olympic rower from Oxford University, has stated she does see benefits for performance and has personally done a study showing decreased hunger on ketones as well as worked with elite athletes who report improved recovery on ketones. I have no reason to doubt her intelligence or integrity. My experience has been the same.

"Using ketones around exercise in terms of recovery, anti-inflammatory and "just" general health and wellness I think is a really, really interesting application, I know that some of the strength and conditioning coaches that I've been fortunate enough to talk to from different pro-sport teams have been much more excited about that as a strategy, more so than performance.... Consistency is key... Being able to take something that has a systemic wellness effect, with anti-oxidant effect and anti-inflammatory effect is very interesting." The debate has got hot-headed about teeny weeny margins in performance... the biggest effect is for everyone else for wellness and avoiding sarcopenia."

Brianna Stubbs

Ketogenic diet athletes will use exogenous ketones very well.

Most critics have never tested the products and refuse to try them.

"Normal people are making money, ketones it must be a lie."

People of poor health are reporting wellness and claiming it’s the ketones, does it have to be a placebo? Let's look at the research.


Are the fitness orthodoxy equally passionate in protesting about coke, mars, cereal, alcohol, cigarettes, opioids? Credit to Greg Glassman, he is taking a stance against health-damaging substances.

Are all the processed foods on supermarket shelves and at bottle shops double-blind tested as healthful / not harmful?

Are the cocktails of pharmaceuticals being prescribed safe?

Surely we have more obvious targets for activism.

“Ok. But all the research isn’t in for every application!”

Is it in for Coke and Red Bull?

Let’s look at what research we have and see if the wave of hate and insults can be justified intellectually. We make our own decisions about what we want to put into the world.


NETWORK MARKETING

KetoMAX is $10 for a single serve in Australia! I thought nobody would buy it.

You’d have to be a great salesperson to sell something that isn’t alcohol for $10 a serve!

Or you would have to speak to people who have tried everything and are still suffering, you will only make one sale to desperate people, if they don’t get a result they won’t buy again and they will defame the product. This hasn’t happened the product has spread virally despite the google optimisation of negative posts.

I can guarantee you the people I work with aren’t great at sales. They’re everyday Joe’s who like the stuff and wanted to tell their friends about it. They are morally and intellectually ok with network marketing.

Tony Robbins, Richard Branson, Robert Kiyosaki and Bob Proctor are all backing network marketing as a great place to start in business and the most honest system of reward. You don't pay for marketing and celebrity endorsement, you do pay your friend who did the marketing leg-work.

What research have you done to disagree with them?

Before throwing stones at network marketing learn from these world leaders. I agree that no sales model is great if the product isn't good.

Lets anaylse the product.


KETONE BODIES

Beta-Hydroxybutyrate, BHB, R-BHB, Ketone Salts, Ketone Esters.

Periods of “keto diet” work for a bunch of things. This is clear in the research and increasingly acknowledged by the medical community. (see research below)

D-BHB is fairly widely accepted to be the most active energetic component of the ketogenic process.

D-BHB is produced in the liver every day.

Under various circumstances production increases. These circumstances include - fasting, extreme exercise where fuel is lacking, calorie restriction and very low carb diets.

Other ketone molecules and elimination of carbohydrates are also players in this conversation but R-BHB has been fairly well accepted to be the greatest influence on the outcomes of the ketongenic diet.

So the question emerges, what happens when you deliver R-BHB either alone or in a cocktail of supporting compound?

Researchers are studying BHB's impact on blood sugar management, endurance, pain tolerance, problem-solving, stress tolerance, blood gas tolerance, lactate tolerance, depression, anxiety, brain development, post-traumatic brain injury and many other areas.

The scientific process is slow, bumpy and not without corruption and human error (Minute 52 - specifically in relation to ketone research). Massively flawed studies have shaped fat and cholesterol consumption for decades. Still, there is value in research and we get clues from each paper that emerges.


Most of the ketone research is being done as n=1. Some people in the science orthodoxy don’t like or care about n=1 experiments but it in the end science is done to help individuals, n=1. If a substance helps one person then it helps them. If it doesn’t help the next that doesn’t change the outcome for the first.

But are there any possible mechanisms in the literature for the benefits people are reporting for KetoMAX?

The following is BHB research. Some are in animal studies (generally done before human trials to prove that a human trial should follow or when killing the subjects is required), some are in petri-dishes, some are in humans. Some of the studies are under ketogenic diet conditions where the researchers have identified BHB as the cause of the results. Some of the studies are with KetoMAX, some are with Ketone Esters (new to market, much more expensive than salts and foul tasting), some are with IV ketone salts.


Is there more or less evidence to support taking BHB than most health supplements?

Is there more or less evidence to support taking BHB rather than investing in coke, beer, smokes, drugs, gambling and junk food?

My grandparents died with cancer, dementia and muscle wasting related to lung function.

My intention is to have higher function for longer than they did and to help others who want to live their best.

Does the science say I’m crazy in thinking that R-BHB could help me live better?


CONCLUSION

I decided long ago to fight for what I believe is right, to decrease suffering and increase the expression of human gifts. This is very clear from how I invested my life prior to ketones and beyond question to reasonable humans. I am no saint. I have had many mistakes, had failures and have done things I’m not proud of. That doesn’t take away from the path I chose long ago that I have continued to walk. People who know me know this is true whether they like me or not.

I have made a lot of money from exogenous ketones. I’m ok with that. Everyone has to make money to live in the 21st century. I believe that I’ve found one of the best and most noble ways to make money. I have thousands of people who can personally attest to the value of the decision I made. Do you have the same support for how you're living?

The decision to back ketones, after success in various other endeavors, wasn’t without risk. I have been heavily criticised many times. Sometimes by friends and family, sometimes by people who I respect highly, often by complete strangers.

Must we ignore that the market has decided it likes ketones? I’m part of what I believe will be the most successful network marketing company ever. This is not a strong argument but it's worth considering with the records Pruvit is breaking.

Should we ignore the hundreds of thousands of customers and at least tens of thousands of business owners who stand by the results they’ve had with this product? Very cynical but I can understand your position in a world of lies.

Can you also ignore that the science world is producing massive amounts of positive data around BHB?

If upon reviewing this body of research you don’t want to test KetoMAX, power to you. If you still feel the need to ridicule it and belittle those who are getting the results that the research suggests, I’m not sure what more I can do to help you.

"One needs in their own life to make choices based on the current best information and reasonable people can have different standards of evidence but I'm confident the we will be waiting a very long time for some of these studies to be done conclusively in humans, perhaps longer than any of us have, certainly me, so, of course there is the need for more research needed and it's going to happen but speaking for only myself I am much more impressed with these animal model research studies than many of the epidemiological studies of humans which are often taken much more seriously than they should be."

Dr Kenneth Ford - Inventor Hall Of Fame / NASA / National Science Board. Stem Talk Podcast,. World leading science with many ketosis and ketone related podcasts.


Ketone Bodies Mimic the Life Span Extending Properties of Caloric Restriction (2017)

https://iubmb.onlinelibrary.wiley.com/doi/pdf/10.1002/iub.1627

The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis.

We hypothesize that increasing the levels of ketone bodies will also extend the life span of humans and that calorie restriction extends life span at least in part through increasing the levels of ketone bodies. An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging-related disorders.


Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. (2014)

https://www.ncbi.nlm.nih.gov/pubmed/24598140/

Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

This study is about ketone esters which give a higher dose of ketones, the ketone salt market has opened the way for ketone esters which may or may not be a better option. Chasing ketones in the blood is not the goal. The goal is cells using BHB and receiving all the signaling effects. The optimal dose for therapeutic effect is not clear. It’s possible that consistent smaller doses will provide the same benefits.


Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats (2016)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743170/


Exogenous ketone supplementation caused a rapid and sustained elevation of βHB, reduction of glucose, and little change to lipid biomarkers compared to control animals. (2016)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743170/#


Conclusions

This study demonstrates the efficacy and tolerability of oral exogenous ketone supplementation in inducing nutritional ketosis independent of dietary restriction.

First in Rats…


On the Metabolism of Exogenous Ketones in Humans (2017)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670148/

Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC.

All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal.

Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.

Then in humans… controlling blood sugar is a key challenge for humanity in an increasingly pre-diabetic world.


Cerebral ketone metabolism during development and injury. (2012)

https://www.ncbi.nlm.nih.gov/pubmed/22104087b

Cerebral metabolism of ketones is a normal part of the process of brain development. While the mature brain relies on glucose as a primary fuel source, metabolism of ketone bodies remains an alternative energy source under conditions of starvation. The neuroprotective properties of brain ketone metabolism make this alternative substrate a viable therapeutic option for various pathologies. Since the ability to revert to utilizing ketones as an alternative substrate is greatest in the younger post-weaned brain, this particular therapeutic approach remains an untapped resource particularly for pediatric pathological conditions.

Great hope here for those that like kids! I have 2 so this means the world to me.


Signaling For New Brain Tissue In Mice?

Beta-hydroxybutyrate promotes the expression of BDNF in hippocampal neurons under adequate glucose supply. (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29966721

Neurobiological evidence suggests that the ketone metabolite β-hydroxybutyrate (BHBA) exerts many neuroprotective functions for the brain. The previous study revealed that BHBA could promote the expression of brain derived neurotrophic factor (BDNF) at glucose inadequate condition. Here we demonstrated that BHBA administration induced the expression of BDNF in the hippocampus of mice fed with normal diet. In vitro experiment results also showed that 0.02-2 mM BHBA significantly increased BDNF expression in both the primary hippocampal neurons and the hippocampus neuron cell line HT22 under adequate glucose supply. Bdnf transcription induced by BHBA stimulus was mediated through the cAMP/PKA triggered phosphorylation of CREB (S133) and the subsequent up-regulation of histone H3 Lysine 27 acetylation (H3K27ac) binding at Bdnf promoter I, II, IV, and VI. Moreover, BHBA stimulus induced a decrease of tri-methylation of H3K27 (H3K27me3) binding at the Bdnf promoters II and VI and the elevation of H3K27me3-specific demethylase JMJD3, which also contributed to the activation of Bdnf transcription. These results demonstrated that BHBA within the physiological range could promote BDNF expression in neurons via a novel signaling function. Moreover, BHBA might possess more broad epigenetic regulatory activities, which affected both the acetylation and demethylation of H3K27. Our findings reinforce the beneficial effect of BHBA on the central nervous system (CNS) and suggest that BHBA administration with no need for energy restriction might also be a promising intervention to improve the neuronal activity and ameliorate the degeneration of CNS.

So you read that BHB is helping grow new brain cells and you find out someone in your family has Alzheimer’s but can’t / won’t change their diet. What if you also had a friend use exogenous ketones and her mum showered herself again and could find her way around the house again. Would you encourage your loved one to try a great tasting drink?


Booster Ketones: Battling Hunger – Hunger Hormones and Exogenous Ketones (Jan 2018)

http://exogenousketones.net/ketones/booster-ketones-battling-hunger-hunger-hormones-and-exogenous-ketones/

Highly interesting, in this author’s opinion, is the good correlation between blood BHB and subjective hunger data. These results suggest that the level of blood BHB may be a pillar in appetite control during a diet protocol.

Hunger was impacted. More research always wanted and needed.


Regional cerebral effects of ketone body infusion with 3-hydroxybutyrate in humans: Reduced glucose uptake, unchanged oxygen consumption and increased blood flow by positron emission tomography. A randomized, controlled trial. (Feb 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29489818

Ketone bodies are neuroprotective in neurological disorders such as epilepsy. We randomly studied nine healthy human subjects twice-with and without continuous infusion of 3-hydroxybutyrate-to define potential underlying mechanisms, assessed regionally (parietal, occipital, temporal, cortical grey, and frontal) by PET scan. During 3-hydroxybutyrate infusions concentrations increased to 5.5±0.4 mmol/l and cerebral glucose utilisation decreased 14%, oxygen consumption remained unchanged, and cerebral blood flow increased 30%. We conclude that acute 3-hydroxybutyrate infusion reduces cerebral glucose uptake and increases cerebral blood flow in all measured brain regions, without detectable effects on cerebral oxygen uptake though oxygen extraction decreased. Increased oxygen supply concomitant with unchanged oxygen utilisation may contribute to the neuroprotective effects of ketone bodies.


Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/29955649

This pilot trial justifies KD studies in mild Alzheimer's disease.

Maybe the BHB is causing BDNF and helping AD brains? Maybe not. When the BHB stopped they regressed.


Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats. (2016)

https://www.ncbi.nlm.nih.gov/pubmed/27999529

We conclude that ketone supplementation may represent a promising anxiolytic strategy through a novel means of inducing nutritional ketosis.

Great news for the suffering rats! Even better for my friends who report that they have a rat-like response to BHB. It’s not a placebo for the rats.


D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. (2003)

https://www.ncbi.nlm.nih.gov/pubmed/12975474

Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD.


Case Studies of Parkinson's patients on Exogenous Ketones

Case Study 1

A recent case study report has looked at the use of ketone salts being given to one participant carried out at the ASPI facility in Tampa, Florida. An individual who has had Parkinson’s Disease for the past 20 years was given a dose of 10 g of beta hydroxybutyrate salts.

The participant was measured using an eye tracking device that measures abnormal eye movement, a characteristic in Parkinson’s Disease. The average score for individuals his age is 17, before supplementation he scored 6 on the scale. After supplementation with the exogenous ketone salts, he scored an average of 18 and reported shaking in his hands had stopped.

Case Study 2

Another similar case study was seen in a gentleman who was classed as disabled in 2014. After 6 weeks of taking exogenous ketone salts, coupled with intermittent fasting and a more paleo based form of ketogenic diet, he noticed marked improvements in his Parkinson’s Disease.

Before using the exogenous ketones his rating on the Unified Parkinson’s Disease Rating was that of 3/4. Now with the ketone salts, it sits at 1/2. What is important to note from this case study though is that he still continued with his standard medication. He did report that anytime he missed medication, he would find the symptoms returning. The exogenous ketones are not “curing” the disease, but in adjunct, with standard care, it appears to be improving them.

Again, when interviewing the case study individuals, there was a clear consensus that for many, using an external aid such as coconut oil or MCT did appear to offer greater symptom relief.

Whilst the animal data and now emerging case studies of the use of ketone salts and esters is promising, it is still very early data.

One of these is soneone I know personally, n=1 matters very much in science and it life.


β-hydroxybutyrate alleviates depressive behaviors in mice possibly by increasing the histone3-lysine9-β-hydroxybutyrylation (2017)

https://www.sciencedirect.com/science/article/pii/S0006291X17311051?via%3Dihub

We showed that H3k9bhb played a role in depression, and firstly linked BHB and BDNF via H3k9bhb. Our findings emphasized the crucial role of metabolic regulation on epigenetics in depression.

Great news for the suffering rats! Even better for my friends who report that they have a rat-like response to BHB. It’s not a placebo for the rats.


Potential Synergies of β-Hydroxybutyrate and Butyrate on the Modulation of Metabolism, Inflammation, Cognition, and General Health (2018)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902005/

The low-carbohydrate high-fat diet (LCHFD), also known as the ketogenic diet, has cycled in and out of popularity for decades as a therapeutic program to treat metabolic syndrome, weight mismanagement, and drug-resistant disorders as complex as epilepsy, cancer, dementia, and depression. Despite the benefits of this diet, health care professionals still question its safety due to the elevated serum ketones it induces and the limited dietary fiber. To compound the controversy, patient compliance with the program is poor due to the restrictive nature of the diet and symptoms related to energy deficit and gastrointestinal adversity during the introductory and energy substrate transition phase of the diet. The studies presented here demonstrate safety and efficacy of the diet including the scientific support and rationale for the administration of exogenous ketone bodies and ketone sources as a complement to the restrictive dietary protocol or as an alternative to the diet. This review also highlights the synergy provided by exogenous ketone, β-hydroxybutyrate (BHB), accompanied by the short chain fatty acid, butyrate (BA) in the context of cellular and physiological outcomes. More work is needed to unveil the molecular mechanisms by which this program provides health benefits.

Franco Cavaleri and Emran Bashar in the Journal Of Nutrition and Metabolism er bold enough to suggest (as Brianna Stubbs Ph.D has in part) that exogenous ketones provide synergy for overcoming metabolic syndrome, weight mismanagement, and drug-resistant disorders as complex as epilepsy, cancer, dementia, and depression! Definitely a cause worth exploration and something which is backed up in the anecdotal evidence and case studies.


Do ketone bodies mediate the anti-seizure effects of the ketogenic diet? (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29325899

Specifically, β-hydroxybutyrate has been shown to interact with multiple novel molecular targets such as histone deacetylases, hydroxycarboxylic acid receptors on immune cells, and the NLRP3 inflammasome. Clearly, as a diet-based therapy is expected to render a broad array of biochemical, molecular, and cellular changes, no single mechanism can explain how the KD works. Specific metabolic substrates or enzymes are only a few of many important factors influenced by the KD that can collectively influence brain hyperexcitability and hypersynchrony. This review summarizes recent novel experimental findings supporting the anti-seizure and neuroprotective properties of ketone bodies.

Ketones are proven in humans to change the brain with “anti-seizure and neuroprotective” effects. Interesting! One study.


Ketone Bodies as Anti-Seizure Agents. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28397070

Nevertheless, the notion that KB are themselves, anti-seizure agents, requires clinical validation, as prior studies have not revealed a clear correlation between blood ketone levels and seizure control. Notwithstanding this limitation, there is growing evidence that KB are more than just cellular fuels, and can exert profound biochemical, cellular and epigenetic changes favoring an overall attenuation in brain network excitability.

Ketones are proven in humans to change the brain with “anti-seizure and neuroprotective” effects. Interesting! Two studies.

It’s becoming well accepted in the research that seizures and neuroprotective effects are mediated by ketones. If seizures are a continuum of brain hyperexcitation then it makes sense that people without epilepsy can also benefit from ketones neurologically. If we know that the ketogenic diet is positive for many other neurological conditions is there a suspicion that ketone salts might help these people. Would a case study on Parkinson’s using ketones influence your view on this. I find great hope here! Do you?


Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28510035

CONCLUSION:

3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.

Ketone bodies don’t solve everything for everyone. That doesn't make them a scam?


Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29446830

And the world leader in ketosis (Dr Dom D’Agostino) just said publicly that his tests have proven exogenous ketones are more powerful than metformin in lowering blood sugar. This should be front page news. Why is it not? Do ketone salts have the same impact as esters? Get a blood glucose meter and test? This is very, very exciting news for a prediabetic planet. Once blood sugar is under control discipline is much easier to find. This is one of the proposed mechanisms for the long-term success of Intermittent fasting, time restricted feeding and the periodic fasting integrated into religions throughout history and now well accepted through the research of Dr Jason Fung and many others.


Intermittent metabolic switching, neuroplasticity and brain health (2018)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913738/

Conclusions and Future Directions

The evidence reviewed in this article leads to several general conclusions regarding IMS and neuroplasticity. First, cognition, sensory–motor function and physical performance can be enhanced by IMS protocols involving IF and/or vigorous exercise. Second, by providing an alternative energy source and activating signalling pathways involved in neuroplasticity and cellular stress resistance, the ketone BHB plays a particularly important role in neuronal adaptations to fasting and exercise.

Because of the criticality of ketones for survival during fasting, such experiments will require ‘titration’ of circulating ketone levels by administration of exogenous ketones.

Several randomized controlled trials of IF in subjects with or at high risk of a neurological disorder are in progress, and results will be forthcoming.

Researchers think there is justification in the research for intermittent fasting and periodic fasting together with BHB supplementation. What they will prove over the years to come could be that the KetoReboot or similar dosing of R-Salt ketones support medicinal fasting.


Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes (2016)

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30355-2

We have demonstrated the metabolic effects of elevated circulating ketone bodies as a fuel and biological signal to create a unique physiological condition. Ketosis may alter substrate competition for respiration, while improving oxidative energy transduction under certain conditions, such as endurance exercise. Consequently, nutritional ketosis may help to unlock greater human metabolic potential.

There are only around 6 studies on ketones and performance so far. This is the most positive. Dr Dom has outlined why the dose and product selection in some of the studies might have interfered with results. Ultimately this is a very small fraction of what BHB is being used for. The other potential benefit is around recovery and general well-being or related to mood and training tolerance. Some of the world’s most progressive sporting organisations are using ketones. They’re not public about why because they want to maintain their competitive advantage as long as possible. It’s quite easy to test efficacy in elite environments and the data is a lot better than pulling together some college students if you’re interested in elite performance. Another exciting application for sports is around head trauma and recovery from extreme trauma. Seeing the research it’s clear that many mechanisms exist for why athletes are continuing to use ketones as a tool.


Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species. (2015)

https://www.ncbi.nlm.nih.gov/pubmed/25649993

Brain cells experience experience hypoglycemia after head injury when insulin is unable to cross the blood brain barrier. Here is a mechanism by which ketones could be helping recovery and repair.


β-Hydroxybutyrate: A Signaling Metabolite. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28826372

Various mechanisms in the mammalian body provide resilience against food deprivation and dietary stress. The ketone body β-hydroxybutyrate (BHB) is synthesized in the liver from fatty acids and represents an essential carrier of energy from the liver to peripheral tissues when the supply of glucose is too low for the body's energetic needs, such as during periods of prolonged exercise, starvation, or absence of dietary carbohydrates. In addition to its activity as an energetic metabolite, BHB is increasingly understood to have cellular signaling functions. These signaling functions of BHB broadly link the outside environment to epigenetic gene regulation and cellular function, and their actions may be relevant to a variety of human diseases as well as human aging.

If KetoMAX is considered only considered as 45 cals which could interfere with fat burning then we are ignoring a large body of research pointing to a broader systemic impact.


β-hydroxybutyrate: much more than a metabolite. (2014)

https://www.ncbi.nlm.nih.gov/pubmed/25193333

The ketone body β-hydroxybutyrate (βOHB) is a convenient carrier of energy from adipocytes to peripheral tissues during fasting or exercise. However, βOHB is more than just a metabolite, having important cellular signaling roles as well. βOHB is an endogenous inhibitor of histone deacetylases (HDACs) and a ligand for at least two cell surface receptors. In addition, the downstream products of βOHB metabolism including acetyl-CoA, succinyl-CoA, and NAD+ (nicotinamide adenine dinucleotide) themselves have signaling activities. These regulatory functions of βOHB serve to link the outside environment to cellular function and gene expression, and have important implications for the pathogenesis and treatment of metabolic diseases including type 2 diabetes.


Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. (2013)

https://www.ncbi.nlm.nih.gov/pubmed/23223453

We report that the ketone body d-β-hydroxybutyrate (βOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous βOHB, or fasting or calorie restriction, two conditions associated with increased βOHB abundance, all increased global histone acetylation in mouse tissues. Consistent with increased FOXO3A and MT2 activity, treatment of mice with βOHB conferred substantial protection against oxidative stress.

Chronic oxidative stress is a risk factor for disease. While this study is in mice it does present another mechanism for some for what we are seeing anecdotally and has been mentioned by Brianna Stubbs as one reason people might take R-ketone salts.


The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury. (2014)

https://www.ncbi.nlm.nih.gov/pubmed/24721741

The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans.

This is a foundation for why athletes and others suffering head trauma should be considering KetoMax. The question is only about the method not the efficacy in this study. What could this mean for the pre-diabetic brain that isn’t responding to insulin (cells aren’t being fuelled)?


Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. (2005)

https://www.ncbi.nlm.nih.gov/pubmed/16180224

More good news for the rats, maybe for the NRL players and boxers too. If nobody was saying they weren’t safe and people had been dosing on them for years, would you take them if you had a brain injury that was impacting your quality of life?


Obligate role for ketone body oxidation in neonatal metabolic homeostasis. (2012)

https://www.ncbi.nlm.nih.gov/pubmed/21209089

These results indicate the critical metabolic roles of ketone bodies in neonatal metabolism and suggest that distinct tissues exhibit specific metabolic responses to loss of ketone body oxidation.

Ketone bodies are acknowledged as critical for babies. Are ketones higher in breast fed children? You can see in the other studies that oral BHB restores brain development in hyperinsulinaemic babies. Ketones are clearly a very important part of human evolution. Is it a mistake that most adults brains are receiving negligible BHB after birth or when breastfeeding ends?


Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. (2011)

https://www.ncbi.nlm.nih.gov/pubmed/21791085

In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways.

Specific cancer applications. Very exciting. Together with the glucose controlling effects, the impact of fasting on cancer cells and the application of ketones together with modern cancer therapy it’s understandable why Dr. Dom D’Agostino is traveling the world speaking to doctors about its application. Statistically, a lot of us will get cancer. It’s happened too much in my family. This research is very interesting.


The Ketone Metabolite β-Hydroxybutyrate Attenuates Oxidative Stress in Spinal Cord Injury by Suppression of Class I Histone Deacetylases. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28683591

The ketone metabolite β-hydroxybutyrate (βOHB), is reported to be neuroprotective after spinal cord injury (SCI) in rats, but the underlying mechanism remains unknown. Therefore, the ketone metabolite βOHB may be a novel promising therapeutic agent for SCI.


Ketogenic Metabolism Inhibits Histone Deacetylase (HDAC) and Reduces Oxidative Stress After Spinal Cord Injury in Rats. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/29024787

More good news for rat lovers! Why do scientists invest so much time in helping rats when we have all these human problems to solve?


A Ketogenic Diet Increases Brown Adipose Tissue Mitochondrial Proteins and UCP1 Levels in Mice (2013)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821007/

Not much to see here more research would be interesting around BHB and brown fat.


Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet (2012)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360149/

There is a study about exogenous ketones and brown fat. Could be something interesting here. Does brown fat mean anything?


Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat (2013)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821009/

Ending insulin resistance, that sounds good. Lucky rats! Do humans have the same response as rats to BHB in any of these R-BHB studies?


β-Hydroxybutyrate: A signaling metabolite in starvation response? (2016)

https://www.ncbi.nlm.nih.gov/pubmed/27083590

It’s not just calories, BHB is a signaling molecule.


A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat. (2010)

https://www.ncbi.nlm.nih.gov/pubmed/20529850

R-BHB decreases food intake in our furry friends. It does the same in humans attempting a 60 hour keto reboot. Brianna Stubbs saw the same in humans and it has been reported by researchers across many trials. Anecdotally BHB makes it possible, if not easy, for 40,000 people, many of whom are likely insulin resistant & overweight to voluntarily navigate 60 hours on 500 calories.


Evaluation of novel formulations of d-β-hydroxybutyrate and melatonin in a rat model of hemorrhagic shock. (Jun 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29936200

BHB/MLT/PVP and BHB/MLT/CD constitute promising candidates for clinical hemorrhagic shock treatment.

BHB + Melatonin for massive bleeding injury. What about minor tissue damage? Here is a mechanism why we have many masters level CrossFit athletes (especially femzles including Australa's best - Amanda Allen) reporting improved recovery on ketones.


Small-volume d-β-hydroxybutyrate solution infusion increases survivability of lethal hemorrhagic shock in rats. (2010)

https://www.ncbi.nlm.nih.gov/pubmed/20386494


D-β-Hydroxybutyrate and melatonin for treatment of porcine hemorrhagic shock and injury: a melatonin dose-ranging study. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/29187245

Getting much closer to humans. It works in pigs too.


Influence of Exogenous β-Hydroxybutyrate on Walking Economy and Rating of Perceived Exertion. (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29953297

This study investigates the effect of a supplementary ketone, β-hydroxybutyrate (BHB), on walking economy and ratings of perceived exertion in apparently healthy individuals. In a repeated-measures, crossover design, ten non-aerobically trained participants (three males; seven females) performed two stages of a duration-modified Bruce treadmill protocol. Participants blindly consumed either 1 ounce of an exogenous BHB solution (KETO) or a noncaloric placebo (CON) 30 minutes prior to exercise testing. Blood ketone and glucose concentrations were measured prior to supplementation (baseline), immediately before exercise, and after exercise. Oxygen consumption (VO2), respiratory exchange ratio (RER), energy expenditure (EE), and rating of perceived exertion (RPE) were recorded during the last two minutes of each stage. Blood BHB concentrations were significantly elevated at the pre-exercise and postexercise time points as compared to the CON condition (p < .001), and blood glucose was significantly elevated postexercise in both conditions as compared to baseline levels (p < .001). No significant between-trial differences (p > .05) were found for VO2, RER, EE, or RPE. The intervention of this study did not produce evidence of an ergogenic benefit from BHB supplementation in a healthy subject pool.

But these ketones didn’t help people walk with less perceived effort… no details of if they used KetoMax or not. Not sure how what the motivation for a walking study might have been. I think we will see something similar to the BHB+melatonin, Sodium bicarb + caffeine scenario where synergy matters for performance.


Intermittent Running and Cognitive Performance after Ketone Ester Ingestion. (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29944604

Compared to carbohydrate alone, co-ingestion of a ketone ester by team sport athletes attenuated the rise in plasma lactate concentrations but did not improve shuttle run time to exhaustion or 15 m sprint times during intermittent running. An attenuation of the decline in executive function after exhausting exercise suggests a cognitive benefit after KE ingestion.

Very unlikely to be keto max based on the gastro response, interesting study model. Not very relevant to the non-athletic population or for athletes looking for overall well-being / neuroprotective benefits.


Effect of acute ingestion of β-hydroxybutyrate salts on the response to graded exercise in trained cyclists. (2018)

Gastrointestinal symptoms were reported in 13 out of 19 participants during KET. Acute ingestion of βHB salts induces nutritional ketosis and alters the metabolic response to exercise in trained cyclists. Elevated RER during KET may be indicative of increased ketone body oxidation during exercise, but at the plasma βHB concentrations achieved, ingestion of βHB salts does not affect lactate appearance, perceived exertion, or muscular efficiency.

Will anyone test the caffeinated version with a couple of weeks for the cells to get used to a fuel they’re not adapted to using? We might see different performance data when those tests are done. 1% of the population really cares about increased race times, 50%+ have serious brain and metabolic dysfunction currently or in the future.


Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists (2017)

Vomitting and GI distress impairs performance in cyclists (Dr Ken Ford) Coke + Esters: Bad research (paper cited by Menno in discreditting the Keto Reboot)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660098/

To understand why the AIShave been criticised for this study hear 3 Ph.D scientists discuss the study - 61 minutes in.


The Role of Microbiota in Depression - a brief review. (June 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29930222

The microbiota-gut-brain axis is a bidirectional homeostatic route of communication between both of the organs direct via receptors of the CNS or via epigenetic mechanisms of diverse metabolites e.g. SCFA, GABA, β-hydroxybutyrate. Thus, a modulation of gut microbiota via nutrition, lifestyle etc. might be effective for emotional status and depressive disorders. The dietary composition has an influence on gut microbiota composition, microbial metabolite profile and the according consequences on emotional status and depression within a system biologic approach. There are changes in gut microbiota composition and gut microbial profile (butyrate, GABA, β-hydroxybutyrate) effecting epigenetic regulation (histone acetylation, DNA methylation) and gene expression of receptors and mediators (SLC6A4, BDNF, GABA, GPRs) involved in depressive disorders.

This is big news. This concept could change the world!


Medium-Chain Fatty Acids, Beta-Hydroxybutyric Acid and Genetic Modulation of the Carnitine Shuttle Are Protective in a Drosophila Model of ALS Based on TDP-43. (May 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29904341

Not sure if this one relates to be honest. BHB acid..?? Anyone? Pretty cool anyway.


The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review. (Mar 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29576959

Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that have typically were not designed to evaluate these variables as primary outcomes, and thus, more research is required to elucidate the role that supplementation might play in encouraging ketogenesis, improve time to NK, and reduce symptoms associated with keto-induction.

My friend ordered 2 boxes yesterday to start this very research! In fact he did the same study 18 months ago and decided it’s time to get back onto the keto diet again. He uses the ketones to on-ramp. Repeatability of results makes for good science.


The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. (2015)

https://www.ncbi.nlm.nih.gov/pubmed/25686106

Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.

Researchers connecting the dots!


β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28249154

BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1β in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.

Again researchers are clear that BHB is making all the difference. It’s a great day for rats! When will they start to care about all the humans with gout!?


How Can a Ketogenic Diet Improve Motor Function? (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29434537

In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and spinal cord injury.

Maybe this is part of why I can 5-ball juggle and handstand?


Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. (2013)

https://www.ncbi.nlm.nih.gov/pubmed/24223849

These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited.

Hospital food for people with brain injuries, something we should change?


The Ketone Body, β-Hydroxybutyrate Stimulates the Autophagic Flux and Prevents Neuronal Death Induced by Glucose Deprivation in Cortical Cultured Neurons. (2016)

https://www.ncbi.nlm.nih.gov/pubmed/26303508

More links between the insulin deprived brain and BHB. Autophagy has been linked to the function of stem cells which are highly related to our capacity for growth and repair.


Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. (2002)

https://www.ncbi.nlm.nih.gov/pubmed/12149510

Baby brains and ketones! This is one of my favourite studies for oral BHB in humans.


Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, β-amyloid toxicity, and astrocyte function. (2015)

https://www.ncbi.nlm.nih.gov/pubmed/25832906

Diet supplementation with ketone bodies (acetoacetate and β-hydroxybuturate) or medium-length fatty acids generating ketone bodies has consistently been found to cause modest improvement of mental function in Alzheimer's patients. It was suggested that the therapeutic effect might be more pronounced if treatment was begun at a pre-clinical stage of the disease instead of well after its manifestation. The pre-clinical stage is characterized by decade-long glucose hypometabolism in brain, but ketone body metabolism is intact even initially after disease manifestation.

If Alzheimer’s is a continuum and the process starts well before diagnosis, would you drink the thing that is causing improvement anecdotally and showing up in research? There are multiple options here MCT, Keto Diet, KetoMax. Should R-BHB be something that aging humans (30, 40, 50?) or humans with brain fog know about and have access to in various forms?


Improved cerebral energetics and ketone body metabolism in db/db mice. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28058963

The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.

More good news for rats, and maybe other mammals with glucose-starved brains! Ketone Bodies are emerging as an exciting metabollic intervention.


A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease. (2015)

https://www.ncbi.nlm.nih.gov/pubmed/25301680

RESULTS:

The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels.

CONCLUSION:

KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet.

So ketones work for Alzheimer’s brains. Esters aren’t practical for many because of price and taste at the moment. What are the other options? If there was a history of this stuff in my family and I wanted to get a headstart but I didn't want to do a Keto Diet, what are my options?


Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. (2012)

https://www.ncbi.nlm.nih.gov/pubmed/22561291

Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet.

Again esters aren’t commercially viable yet. Can you see how a great tasting, affordable R-salts for the mass market could do well?


An Ester of β-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and a Cholesterol Biomarker in Humans.(2015)

https://www.ncbi.nlm.nih.gov/pubmed/26498829

Just another R-BHB success. Humans and rats together… It has the same function in HUMANS and RATS in this study.


Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. (2014)

https://www.ncbi.nlm.nih.gov/pubmed/24598140

Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

Yes exogenous ketones are safe and exciting to those who would like to see a happier healthier planet.


Exogenous administered DL- sodium beta-hydroxybutyrate (beta-OHB) can cross the blood-brain barrier. (2003)

https://www.ncbi.nlm.nih.gov/pubmed/12715792

Yes exogenous ketones are safe, exciting and they make it to your brain.


Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. (1988)

https://www.ncbi.nlm.nih.gov/pubmed/3392207

We conclude that beta-OHB decreases leucine oxidation and promotes protein synthesis in human beings.

Old one about muscle sparing with BHB. Might have some applications for hospital patients, lazy people and even muscle heads.


Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28750585

Ingestion of ketone salts prior to exercise increases fat oxidation during steady-state exercise but impairs high-intensity exercise performance.

2 stories here. One great for humanity one not so. Fortunately, the important one is great! Ketones help adult males (not mice or rats this time) BURN MORE FAT. Someone who loves science more can tell me by how much and we can study how much that number increases over-time with adaptation to burning fat as a fuel which we know is highly adaptable, much more so than processes around glucose metabolism which can’t change by nearly as much.


Effect of ketone infusions on amino acid and nitrogen metabolism in man. (1975)

https://www.ncbi.nlm.nih.gov/pubmed/1133179

It is concluded that increased blood ketone acid levels induced by infusions of Na DL-beta-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation

From the perspective of Gabrielle Lyon’s Muscle-Centric Medicine, these could be important findings, from 1975. Safe important use of ketone salts in humans in 1975.


Effect of a Sodium and Calcium DL-β-Hydroxybutyrate Salt in Healthy Adults. (2018)

https://www.hindawi.com/journals/jnme/2018/9812806/

RESULTS:

The supplement led to a significant increase of D-βHB concentration in blood 2.5 and 3 h after oral intake (p=0.033; p=0.043). The first significant effect was measured after 2 h with a mean value of 0.598 ± 0.300 mmol/L at the peak, which was recorded at 2.5 h. Changes in serum electrolytes and BGA were largely unremarkable. Taking the supplement was not without side effects. One subject dropped out due to gastrointestinal symptoms and two others reported similar but milder problems.

CONCLUSIONS:

Intake of a combination of calcium and sodium D-/L-βHB salt shows a slow resorption with a moderate increase of D-βHB in serum levels. An influence of βHB salts on acid-base balance could not be excluded by this one-dose study. Excessive regular consumption without medical observation is not free of adverse effects. The tested product can therefore not be recommended unconditionally.

This is either the 2016 Pruvit ketones or another brand (It’s D-L rather than D only Keto Max). For this reason quality matters. We did deal with gastro symptoms a lot in 2016 particularly with the first iteration. See below, I’m not making this shit up.


β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. (April 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29705237

CONCLUSIONS:

Collectively, our data shows that BHB production during excess alcohol consumption has an anti-inflammatory and hepatoprotective role through an Hcar2 dependent pathway. This introduces the concept of metabolite-based therapy for AH.

LAY SUMMARY:

Alcoholic hepatitis is a life-threatening condition with no approved therapy that occurs unexpectedly in people who consume excess alcohol. The liver makes many metabolites, and we demonstrate that loss of one such metabolite β-hydroxybutyrate occurs in patients with alcoholic hepatitis. This loss can increase alcohol-induced liver injury, and β-hydroxybutyrate can protect from alcohol-induced liver injury via a receptor on liver macrophages. This opens the possibility of metabolite-based therapy for alcoholic hepatitis.

Do you know anyone who abuses alcohol? I would love to see this on the front page of the newspaper and available in all bottle-shops and bars.


Comparison of lactate and β-hydroxybutyrate in the treatment of concanavalin-A induced hepatitis. (Jun 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29945025

The marked anti-inflammatory properties of combining Lac and BHB were attributed to their cooperation in repressing immune cells (monocytes and neutrophils) infiltration to the liver.


Treatment with D-β-hydroxybutyrate protects heart from ischemia/ reperfusion injury in mice. (Jun 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29679541

Our results indicated that treatment with exogenous BHB protected heart from I/R injury in mice.

Have heart attacks been prevented with BHB supplementation? The market for mice is definitely going to be read hot as this news gets around. Pigs soon!


Ketogenic diet, high-intensity interval training (HIIT) and memory training in the treatment of mild cognitive impairment: A case study. (April, 2018)

https://www.ncbi.nlm.nih.gov/pubmed/29678606

MoCA baseline score was 22/30 (MCI); post-intervention score: 30/30 (normal). MetS biomarker improvements also reflected statistical significance.

Memory experts love ketogenic diet and BHB. Is anyone interested to be one of the first million to experience the benefits of this?


Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease. (2016)

https://www.ncbi.nlm.nih.gov/pubmed/26766547

Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed.


Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease. (2016)

https://www.ncbi.nlm.nih.gov/pubmed/27458340

We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal.


A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease. (Jul 2018)

https://www.ncbi.nlm.nih.gov/pubmed/28709938

DISCUSSION:

This quantitative kinetic PET and MRI imaging protocol for brain glucose and acetoacetate metabolism confirms that the brain undergoes structural atrophy and lower brain energy metabolism in MCI and AD and demonstrates that the deterioration in brain energy metabolism is specific to glucose. These results suggest that a ketogenic intervention to increase energy availability for the brain is warranted in an attempt to delay further cognitive decline by compensating for the brain glucose deficit in MCI and AD.


Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible link to Mild Insulin Resistance - Polycystic Ovarian Syndrome (2015)

https://www.ncbi.nlm.nih.gov/pubmed/26650926

Solving regional glucose hypometabolism as mentioned in many of the other studies has implications for other conditions not yet present in the research.


The β-hydroxybutyrate receptor HCA2activates a neuroprotective subset of macrophages (2014)

https://www.nature.com/articles/ncomms4944

Our data suggest that HCA2 activation by dietary or pharmacological means instructs Ly-6CLo monocytes and/or macrophages to deliver a neuroprotective signal to the brain.

More brain stuff about BHB.


Metabolic characteristics of keto-adapted ultra-endurance runners (2016)

https://www.sciencedirect.com/science/article/pii/S0026049515003340

Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar.

The massive adaptation to fat may also be present and take some time with BHB, or maybe not. It’s clear with endurance performance that chronic adaptation is the key.


Ketogenic Diets and Pain (2013)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124736/

Inflammation is increasingly appreciated as part of the epileptogenic process, and becomes ever more strongly associated with neurological problems in young and old alike. For example, autism is associated increasingly with maternal inflammation,62 and seizures are often comorbid.63 Inflammation and seizures are similarly comorbid with Alzheimer's disease,64, 65 and recent work has highlighted benefits of metabolic therapies in Alzheimer's and Parkinson's disease.66 Recent reviews have highlighted the potential for ketogenic diets in diverse disorders.21, 67 Aside from disease-based processes, cognitive impairment has been observed alongside prediabetes even in adolescents,68 thus underscoring the ability for altered metabolic homeostasis to affect brain function throughout the lifetime. A major research focus should be on how metabolic interventions such as a ketogenic diet can ameliorate common, comorbid, and difficult-to-treat conditions such as pain and inflammation.

In a world where pain medications (opioids) are killing people and destroying lives at something close to the rate of the second world war, we should look at BHB and pain. I have a personal testimony from an orthopedic surgeon of an astonishing atypical recovery from horrific shoulder surgery using the Blue Ocean - high strength Keto Unleashed product. More research is desperately needed here to back up this study using exogenous BHB.


Ketogenic diet in migraine: rationale, findings and perspectives. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28527061

As above, BHB promoters are seeing lives transformed. Research will accelerate the awareness of the medical community.


The promising potential role of ketones in inflammatory dermatologic disease: a new frontier in treatment research. (2017)

https://www.ncbi.nlm.nih.gov/pubmed/28043175

This evidence shows that ketones and the ketogenic diet may have a promising role in the dermatologist's disease treatment repertoire. Our goal is to provide a novel direction for research in the role of a ketogenic diet and even exogenous ketone therapy in the treatment of inflammatory dermatologic disease.

Skin conditions are not superficial in the 21st century. We have seen great changes anecdotally. This paper demonstrates that the science world is eager to catch up.


Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes (2018)

https://www.sciencedirect.com/science/article/pii/S0026049517302986

Compared to a HC (high-carb) comparison group, a 12-week period of keto-adaptation and exercise training, enhanced body composition, fat oxidation during exercise, and specific measures of performance relevant to competitive endurance athletes.

Again an adaptation phase is reported here together with the efficacy of the ketogenic diet. It’s possible that BHB utilisation improves over time.


Ketone Body Infusion With 3‐Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study (2017)

http://jaha.ahajournals.org/content/6/3/e005066

Ketone bodies displace MGU and increase myocardial blood flow in healthy humans; these novel observations suggest that ketone bodies are important cardiac fuels and vasodilators, which may have therapeutic potentials.

Important cardiac fuels! I have a heart and I have ketones!


Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics (2017)

https://www.sciencedirect.com/science/article/pii/S1550413116306556

Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.

Powerful words. The invitation is for you to experience this.


Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress. (2018)

https://www.ncbi.nlm.nih.gov/pubmed/29662437


My hope by the time you read what you need here and discover that there is some link between R-BHB and health. There is also an overlap between rat studies and human studies, there is an overlap between Keto Diets and R-BHB, not 100% but something.

If all this research is false and all the anecdotes I have heard are placebo as well as my own experiences on and off the product over the last 2 years. Then I have made a mistake. The probability of that is low.


The criticism that Caffeine is added to KetoMax.

Firstly coffee is the second most traded LEGAL commodity in the world after petroleum. If you’re protesting against caffeine itself this is not the place for it.

Secondly it’s clear from other studies that synergies matter. We’ve seen that in BHB + melatonin, BHB + lactate etc. Well BHB + Caffeine is also likely a key relationship especially if you want to see an ergogenic effect.

Studies prove BHB works alone, it works better with caffeine.


Effects of sodium bicarbonate, caffeine, and their combination on repeated 200-m freestyle performance. (2008)

https://www.ncbi.nlm.nih.gov/pubmed/18458356

These findings suggest that the ergogenic benefit of taking C alone for repeated 200-m swimming performance appears limited. When combined with NaHCO(3), however, its negative impact on repeated maximal exercise performance is reversed.


Caffeine and Bicarbonate for Speed. A Meta-Analysis of Legal Supplements Potential for Improving Intense Endurance Exercise Performance.

https://www.ncbi.nlm.nih.gov/pubmed/28536531

Thus, caffeine's and bicarbonate's ergogenic effect is clearly documented for intense endurance performance. Importantly, for all supplements an individualized approach may improve the ergogenic effect on performance.


More research to be done here but don’t discount the potential for synergy. Especially when the key researchers have highlighted its importance and there are many other examples of it.


Do L-BHB isomer ketones matter?

They exist within the cells but not in circulation. Prof Veech has spoken out against them but has been asked to show evidence by Dr Dom D’Agostino. Anecdotally people report a much bigger effect from R form BHB taken together with Caffeine. Much greater than 80mg of caffeine alone or R-BHB alone. See the podcast with Oxford Exogenous Ketone Expert Brinna Stubbs.


On the Metabolism of Exogenous Ketones in Humans

https://www.frontiersin.org/articles/10.3389/fphys.2017.00848/full

Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, D-βHB, and L-βHB, despite the metabolism of L-βHB being poorly understood (Webber and Edmond, 1977;Scofield et al., 1982;Lincoln et al., 1987;Desrochers et al., 1992).


COMMON CONCERNS

  • R-BHB is useless!

Please read above and contact all the relevant scientists.

  • Making money from something means you're lying about it!

Ok, this is a deep cynicism. Are you applying this to all purchaces you make and all conversations you're having?

Of all the things to violently oppose in the 21st century why would you choose R-BHB?

  • You just pee it out.

The research shows high absorption and use.

  • Just do Keto Diet

Most of society don't have the baseline will-power and knowledge to get into ketosis. For myself it was a slow grinding process to get keto-adapted. Most people aren't going to get it done or at least they can do with some support and strategies to make it. Pruvit has been the gateway for many people to completey change their diets and lives.

  • It doesn't help people lose fat because it's calories

I have seen a lot of people lose weight. Satiety, improved systemic wellbeing which the PhD reserachers are talking about. Decreased baseline insulin and blood sugar. There are many possible mechanisms. Increased focus and mood is also reported by many people helping them to train better more often.

45 calories is unlikely to make a massive negative impact on fat-loss, energy balance expecially when coupled with the above. We have 40,000 people each month managing a 60 hour reboot consuming only ketones. Something is happening with satiety and brain function or they would not be making it through feeling so great.

Buying a health business also helps a lot of people to get their lives in order to become a great transformation. While it's not what science types want to hear psychology must always be considered as an influence on physiology. This does not void the dozens of studes above.

  • The proprietary formula must be weak!

Yes it’s proprietary so are many brands with a competitive advantage. There are a bunch of BHB ketones in there that show up in the blood and in the improved function associated with this product.

  • Overpriced!

If you consider that all competitors are 50% strength with racemic and non-racemic molecules then that debate is over. I’ve tried lots of other brands to see if they’re equal. They are not. Lots of other people have given the same feedback with no vested interest. Believe me or test them yourself. L-BHB doesn't naturally circulate and tends to be in the blood longer (showing that it's not used). Why is L-BHB 50% of competitor products? Because it's much cheaper to produce and there is no patent pending as there is with the KetoMaX

  • Not all the benefits people are experiencing are confirmed in double-blind studies yet.

TRUE, more research needed but there is a tonne of clues in the research above and science is working hard to catch up.

  • We don’t need to be ingesting the L-molecule since it’s not produced by the liver (Keto Max doesn’t contain the non bio-identical form like other brands)

Prof. Veech has argued this, he might be right. Certainly the impact from the R-BHB seems to be felt more and is demonstrated in the ester studies.

  • The benefits aren’t greater than the cost.

OK that’s your judgement call. Some agree, many don’t hence why we have an exploding market.

  • There is caffeine in some versions of the product therefore it’s all the caffeine.

Incorrect see above. I've used 300mg caffeine drinks with much less impact than 80mg of caffeine with a good dose of R-BHB.

  • Salt is ergogenic, it’s just the sodium.

See above.

  • ATP Science approach - raspberry ketones are bad and these have a similar name so lets muddy the waters together.

Not great science guys, Get Brianna Stubbs or a ketone expert on if you'd like to discuss exogenous ketones legitimately.

  • The dose is too big - Supra-physiological doses.

Take less if you want less, blood readings are physiologically normal personally I agree that Esters would seem ill-suited to daily use for those without disease for this reason. BHB salts create mild ketosis for 2-8 hours.

  • Salt (sodium) is bad

Keep reading, old science / bad medicine, do pay attention to key minerals like magnesium, iodine, iron, copper etc.

  • The dose is too small

Take more / the dose is effective for the intended goal

  • If it's so good why aren't top athletes using it?

They are. I've sold it to a number of world class athletes with good feedback and results. There are many athletes and teams using ketones around the world. As Brianna Stubbs has said many coaches are enjoying the recovery and generaly well being benefits as well as the performance side.


I have decided to help people. The excitement about the research and the thousands of lives changed for the better is clear.

I challenge you to also make the decision to decrease suffering and help people live on purpose in whatever way you see fit.

I conclude together with the research that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.

I’ve been in the best shape of my life on ketones and went beyond that with the keto reboot to 6.8% on the skulpt, way below where I’ve ever been able to get to with every other approach I’ve used.


A Few Top Researchers/Experts Who Are Exploring The Applications of Exogenous Ketones

  1. Dr Dom D'Agostino - Sponsored by the US military for research

  2. Brianna Stubbs - Oxford University PhD

  3. Dr Kenneth Ford  - NASA, Institute for Human & Machine Cognition (IHMC)

  4. Dr Dawn Kernagis

  5. Dr Ryan Lowery

  6. Dr Jacob Wilson

  7. Peter Attia MD

  8. Peter Cox - Oxford University

  9. Lots of the other contributers to the studies above.



Ketones for body composition. Lots of study references here.  Again I can show you my photos for further anecdotal support together with hundreds of others.


This article has links to lots of AC-11 efficacy and safety studies as well as explanations around DNA repair.


I hope this served you and humans in general.

Constructive feedback is welcome!

Facebook / Instagram /  YouTube

This is written as an individual not representing any group or organisation.

 
Keegan Smith