This could be as impactful as the discovery of penicillin
That’s the first thing that comes to mind when learning about the history-altering work of NIH scientist (for over 45 years) Dr. Richard Veech, a man the general public has probably never heard of.
Why haven’t you heard of him? Because he’s dedicated to science, not sales. So, what do scientists and entrepreneurs have in common? They both dedicate their lives to making a difference, discovering ways to make the world operate more effectively. But there’s an important cultural distinction between the two: Entrepreneurs’ success is tied to dollars, while scientists’ success is tied to discovery.
Remember how penicillin altered history? We might be at that moment in history again, but with a “ketone ester” drink invented by Dr. Veech, that has insanely widespread uses. Imagine a drink that could treat Alzheimer’s, Parkinson’s, diabetes, epilepsy, concussions, heart failure, all while helping elite endurance athletes break world records. Then, imagine that it’s a formula perfected over decades, but only now ready in an era where genetics is sexiest of sciences, so this liquid goes underfunded and underproduced. It seems too good to be true, but it’s not. It’s real.
Add to the issue of funding is an overly modest old scientist who said he would literally run if someone called him a hero for his work.
Next, toss in imitation products that use salt-filled caffeinated versions of Dr. Veech’s decades old, already discarded work and you might be left very confused. If a breakthrough sports drink and patient treatment exists, would anyone even believe it?
So what is this ketone ester?
Ketones are human’s back up fuel system that kicks in when humans starve, or at least run out of sugar. The body then burns fat to create an efficient ketone fuel. What many of the therapeutic uses (including Alzheimer’s) have in common is the brain’s blockage of the path to use sugar for energy, meanwhile ketones can bypass this blockage and simply fuels the brain.
Dr. Veech invented a way to bottle that fuel, in a fat-free and salt-free super FDA-approved concentrated food, not a drug. Ketosis is the metabolic state that uses ketones as a primary fuel source, but is mainly known by those that undergo an Atkin-like ketogenic high fat diet. This is drastically different because you get the benefits of ketones without the drawbacks of the high fat. Some call the fat-free version of ketosis, “Veetosis,” in honor of Dr. Veech, the doctor who holds the key to so many treatments.
The catch is that even though billions can be made from this invention, it is unbelievably expensive to make and there’s no funding for an older scientist that doesn’t schmooze. How expensive? For scientific purposes, labs can make a patented product, and for this exact ester they charge $60,000 per 25 mL serving, but with a newly discovered process and an investment, that could drop quickly to $20 a drink.
Absent a single investment, perhaps that can be done via the new world of crowdfunding (or rich, science-inclined geeky startup folks), so hopefully you’ll see Dr. Veech’s ketone ester on shelves sooner rather than later.
The path to the discovery has been long
Dr. Veech worked in 1966 with Dr. Cahill (the man that starved volunteers to prove the brain could run on ketones), and in 1969 under nobel laureate Dr. Krebs (if you took chemistry, you have definitely heard of the Krebs cycle). Dr Veech solved a problem which Krebs delegated to him. Krebs said he must be wrong, only to come back later to co-author the longest paper of Krebs’ career. It was the foundation for understanding why ketones work. Right now, our science geek readers get it – Dr Veech is a pretty big deal, and his work should be taken seriously.
Fast forward to 1995, Dr. Veech co-authored a breakthrough paper on how ketones change metabolism, and in 2000, a paper on Parkinson’s, Alzheimer’s, diabetes, and abolishing the effects of free radical damage.
In 2004, as part of a competition to find a new fuel for the special forces, the U.S. Defense Advanced Research Projects Agency (DARPA), gave a handful of groups $2 million each per year. Only Dr Veech’s group, including Oxford University partner Dr. Kieran Clarke, was left standing. They earned $10 million of total funding, resulting in an FDA-approved food. Who would have guessed DARPA’s role in potentially treating millions of patients with this new food?
A modest scientist does not a salesman make
Even a simple Oxford-approved boxing study to demonstrate ketone ester’s benefits for concussions hasn’t been picked up. One would think a football team owner might want to donate to prove a treatment backed by science that may bring a $20 million a year quarterback that has been earholed, back onto the field a few games earlier. Not to mention, the league could limit the potential liability around debilitating diseases plaguing players decades later.
So the path to the discovery has been long, but anyone we spoke to that was aware of Dr. Veech’s work sung his praises. The challenge is that the older sharp-tongued doctor is hyper-focused on his work, isn’t interested in fame, noting that it is “unseemly for doctors to promote themselves,” and that it is “not part of the job.” Times have changed, and modesty has been replaced by self promotion, as the driver in today’s world of discoveries.
Ketone esters have had success with human testing
In endurance sports, the ketone ester has been proven in a lab to increase output by up to 2%. That can be the difference between a gold and not placing. When tested on 19 elite rowers, there were nine season’s bests, five personal bests and one world record. Only one did slightly worse than the placebo test.
Meanwhile, Dr. Mary Newport was trying to treat her husband with Alzheimer’s and discovered Dr. Veech’s work while digging around in his 20+ patents. She was the author of “Alzheimer’s Disease What If There Was a Cure, The Story of Ketones” about her coconut oil therapy that naturally releases ketones, which she said turned her husband’s “lights back on.” Hundreds have written to her claiming similar results. Ultimately, her husband received Dr. Veech’s ketone ester for a few years and Dr. Newport said it was 10x more effective than the coconut therapy.
Think about that for a minute. The lights came back on! Why is the world not freaking out with excitement!?
Another believer in ketones and Dr. Veech is William Curtis. He has had Parkinson’s for over 15 years, and despite being on the common cocktail of meds, he had tremors, severe muscle spasms, and sometimes stared at the computer screen for hours, nearly frozen. With a little biochem in undergrad, he searched and came across Dr. Veech’s papers, emailed with the doctor, and sought alternative natural ways to raise his ketone levels (also referred to as D-bhb levels).
Dr. Veech told him that absent the availability of clinical trials with the ester, and as long as his primary care doctor approved, Curtis could try a high fat morning drink to increase his ketone levels. After some tweaks and fasting each night, Curtis says his results were stellar. He could concentrate for hours, spasm free, and was able to drive again. Dr. Veech has warned Curtis to watch his cholesterol and to stay on his meds. Curtis continues his routine today, shares his successes online, and plans to continue until the ketone ester is available in clinical trials.
This generation’s most significant medical discovery
The final problem is that scientists write papers and seek grants which don’t require a monetary return on investment; for many it’s just not in their nature to write a business plan and go to a bunch of pitch offs.
We believe that with billions being thrown at sciences like space travel, it seems that investors or Congress should be primed to pump a few dollars into a simple ester to treat a dozen common medical problems that impact all of us as individuals and is nearly bankrupting the country.
We will be following Dr. Veech’s progress (he even finally has his own website), and works as he blazes a path in the scientific community, and hopefully soon, the business community. It is our sincere hope that investors (both government, traditional, and non-traditional) “read the damn papers,” as Dr. Veech says, because we believe that he’s sitting on our generation’s equivalent of the discovery of penicillin. If not bigger.
UPDATE: Dr. Veech is now on Twitter so you can connect with him.
#Veetosis
Lani is the COO and News Director at The American Genius, has co-authored a book, co-founded BASHH, Austin Digital Jobs, Remote Digital Jobs, and is a seasoned business writer and editorialist with a penchant for the irreverent.
A. Will
February 17, 2016 at 7:31 pm
Fascinating
Lani Rosales
February 25, 2016 at 1:53 pm
Agreed!
Britt
February 19, 2016 at 2:34 pm
Interesting question if the body could even use the ketone ester without limiting carbs or glucose present in the blood?
Rob Coberly
February 26, 2016 at 6:32 pm
You may be thinking about hepatic ketogenesis, which is suppressed by carbohydrate intake. Unquestionably many tissues can make immediate use of the dominant circulating ketone body, beta-hydroxybutyrate. This is the substance that is liberated upon absorption of the ester. Veech and Kieran Clarke have published the human studies including pharmacokinetics.
These are fuels that are taken up and enter metabolism freely in proportion to their concentration. There is a monocarboxylate transporter that moves BHB across the blood brain barrier as well. All of that is not suppressed by any other dietary intake.
A good reference is this – “Ketone body metabolism and cardiovascular disease” which covers the general metabolism well.
https://www.ncbi.nlm.nih.gov/pubmed/23396451
Christopher J
February 22, 2016 at 2:15 am
I’ve been thinking exactly this for the last year. Upon the emergency room endocrinologists asking me why I’d want to kill my 7 year old nephew and his kidneys, after I suggested a ketogenic diet when they revealed he in fact had type 1 diabetes, I’ve been researching this metabolic wonder ever since. The author missed one of the biggest target therapies; cancer! We’re talking billions upon billions of dollars. The scope is massive.
Lani Rosales
February 25, 2016 at 1:53 pm
Hey Christopher, thanks for weighing in – Dr. Veech opted not to comment on cancer, and although some people do seem to feel confident in ketones’ potentiality for treatment, I’m sure Dr. Veech has his reasons for not associating the two at this time.
Rob Coberly
February 22, 2016 at 9:15 pm
I strongly agree that investigation into the potential benefits of moderate ketosis for many medical conditions is justified. Moderate ketonemia may be induced by administration of ketone body esters – these are esters of either of the principal ketone bodies, beta-hydroxy butyrate and acetoacetate, usually esterified with butanediol – or by ketone body salts, or medium-chain triglycerides. The esters are most direct and efficient, they have no sodium or potassium load as the salts do, and they do not require the stages of oxidative metabolism followed by hepatic ketogenesis that the MCTs must undergo. The elevated circulating ketone body levels may reach the 2-5 mM range, physiologic as if in a prolonged fasting state, and this state is fundamentally different from the dangerous and pathologic condition of diabetic ketoacidosis.
For decades, much of pharmacotherapy has focused on the more complex molecules that may interact with cell surface receptors, nuclear receptors, or enzymes. We haven’t heard much about these small molecules, the ketone bodies, in medical applications; but thanks to the work of many researchers, there is mounting evidence for potential usefulness in many difficult conditions such as neurodegenerative diseases, inflammatory diseases, and metabolic disorders. The ketone bodies were recognized early on as biologic “substrates and signals”. They are now known to function both as versatile and efficient cellular fuels and as signaling molecules that deliver messages – promoting increases in cell antioxidant capacity, in mitochondrial biogenesis and the “browning” of adipose tissue, and decreases in inflammation, in overexcitation of neurons, and reactive oxygen species generation. When therapeutically employed, the KBs are also likely to support many intracellular functions in various tissues without interference or interaction with most of our commonly employed medications, as the mechanisms of action should be distinct.
In addition to the exogenous ketone approach long championed by Dr Veech, Dr Kieran Clarke and more recently by Dr Dominic D’Agostino, I also support similar broad research into ketogenic and other low-carbohydrate diets. These diets are already known to benefit epilepsy, obesity, mitochondrial diseases, and disorders of insulin resistance. Ketone bodies may be a principal mediator of some of these benefits, but the diet’s decreased reliance on carbohydrate intake and thus glycolysis may also be vital in lowering excessive insulin secretion, preserving the NAD+/NADH ratio in cytoplasm to a range favorable for the epigenetic actions of sirtuins, and decreasing the potentially damaging “reductive pressure” placed on the mitochondrial respiratory complexes by typical “Western” diets. Such low carbohydrate diets are actually not very difficult to follow; anyone interested may consult the published work of Dr Stephen Phinney and Dr Jeff Volek.
Rob Coberly MD
Albuquerque
Angie
February 24, 2016 at 11:09 am
I drink pure therapeutic ketones everyday! Ketones have cleared my mind, given me sustained level energy. I am free from anxiety that I’ve lived with for 17 years. I’m so thankful for these brilliant dedicated scientists!
Jose
February 25, 2016 at 1:46 pm
Angie, the Ketone Esters that are featured here are not available. Do you have a connection with NIH? And if you are taking the “Salts”, perhaps you didn’t read the part about the imitation products mentioned.
Peter H
February 25, 2016 at 2:05 am
I find this line particularly interesting
“toss in imitation products that use salt-filled caffeinated versions of Dr. Veech’s decades old, already discarded work.. ”
Yet those same companies link to this article as if it validates their completely different product. Hum.
I guess the caffeine results in skim reading.
JB
February 25, 2016 at 3:56 pm
There is at least one commercially available supplement that will provide what is generally considered to be a therapeutic level of ketones, demonstrable through any of the usual testing methods. The “salt” is a BHB compound that facilitates delivery of the BHB in a drink mix, and it helps to buffer the acidity of the ketones in the blood as well as help replace salt the body naturally loses in ketosis (elevated ketone levels are known to have a diuretic effect). This is based on a formula patented by Dr Dominic D’agostina and a few others (mentioned in Dr Coberly’s post above). And it’s available without caffeine. So if it delivers the ketones at that level why would it not have value on its own merit, especially given that it’s actually available and affordable? Dismissing it out of hand as an “imitation product” requires some substantiation.
Shane
February 25, 2016 at 11:32 pm
Yes, I take the product with alkaline ionized water. Because a having ketones can lower your blood ph levels. everyone who takes the product should have an ionizer to mix the product.
Rob Coberly
February 26, 2016 at 6:37 pm
Right, KetoCaNa. BHB calcium and sodium salts. And no caffeine. Is the BHB a racemic mixture? I don’t know the answer to that.
JB
February 27, 2016 at 12:35 pm
The one I’m familiar with has only been on the market for a few months and is called Keto//OS. It’s a combination of BHB and a (proprietary I think) MCT powder. Couldn’t tell you whether it’s racemic. It is based on a formula developed at USF on an Office of Naval Research grant by Dr Dominic D’agostina and Angela Poff to reduce incidents of seizures in divers with excellent results. And it does deliver a therapeutic level of ketones (AKA ketosis, just not dietary ketosis). Sounds like a real thing to me so I’m just wondering if there’s a more specific comparison to the esters as far as efficacy, etc.
Peter H
February 26, 2016 at 10:15 pm
He invented the Salts too, 10-15 years ago. If what he found worked, he would have pursued it. But the amount of salt necessary to get bhb levels up enough would require the consumption of about one restaurant salt shaker. Huge difference. There is a reason there is no lab proof of any gain with the salts. Even one study in Europe said bhb didn’t work on a rat study. Oops, they used the Salts. Didn’t work. Won’t magically work on humans.
JB
February 27, 2016 at 12:43 pm
The product I have experience with provides a ketone level in the “ketosis” range (.5 to 5+ mmol) detectable with urine or blood testing. Many of the commonly described characteristics of ketosis are in evidence. So if the BHB and acetoacetate levels are there, what “doesn’t work”? Where is the functional difference?
Rob Coberly
February 27, 2016 at 7:37 pm
I am pleased overall that various products are being marketed and discussed for promoting moderate ketosis. Whether based on MCTs and/or ketone salt mixtures, or based on ketone esters, all should get BOHB and AcAc into circulation to some degree, and all should be safe when properly manufactured. So no one is likely to be hurt by them, the first consideration in medicine. They may differ in efficiency, or in concentration range achieved. The products various parties have been able to bring to market so far are all at an early stage of public experimentation and adoption. Time, experience, and more science will likely tell us what the differences among methods actually mean for health.
I’m not going to tackle in this comment the various reasons to expect that ketosis may promote health and diminish risk for various chronic illnesses. The ketogenic diet, intermittent fasting, calorie restriction, and induced ketosis appear to me to each be distinct but related alterations in diet, energy metabolism and therefore biochemistry. These likely form an overlapping set of interventions. If any of these techniques share common mediators, the ketone bodies would be principal candidates. For many of us there are good reasons to adopt a very low carbohydrate diet, and thus produce our own ketosis by lipolysis, beta-oxidation, and hepatic ketogenesis. Bear in mind that exogenous ketone bodies may downregulate our own lipolysis by the activity of BOHB at the GPR109a receptor on adipose cells.
I’ve been looking at my reference collection to find any documentation pertinent to the issue of BOHB racemic mixtures. This is an issue that conceivably could make a difference in the quality or efficiency of the products we are discussing. D-beta hydroxybutyrate, also described as (R)-3-hydroxybutyrate, is the predominant ketone body in circulation. It is enzymatically interchangeable with (non-chiral, less stable) acetoacetate in a redox reaction that occurs intracellularly and this reaction is the first step toward ketone body oxidation (which will yield acetyl-CoA leading to ATP production via the TCA cycle and oxidative phosphorylation).
So, is L-beta hydroxybutyrate different in any important ways? It would be a component of the synthetic racemic BOHB mixtures. So far I’ve found enough to make me want to continue research on this question. And I’m sure there are knowledgeable individuals who could tell us more.
1-“One of the KB, BHB, is optically active and as the chemically-manufactured form is an equal mixture of the D- and L-isomers. Endogenous BHB is the D-isomer and mammalian tissues have no recognized pathways for conventional oxidation of the L-form (Robinson & Williamson, 1980). This would suggest that half of any administered exogenous BHB may be metabolically useless. …All these studies have used the racemic mixture of BHB and must be interpreted with some caution because of uncertainty about the pathways available for the metabolism of the L-isomer (Robinson & Williamson,1980) which has constituted half the infused load.” from Ketone Bodies As Substrates, Rich AJ, Proceedings of the Nutrition Society, 1990, 49, 361-373.
2- “The ketone bodies enter extra-hepatic tissues on the same carrier, where other monocarboxylates can act as competitive inhibitors. Unphysiological isomers such as D-lactate or (S)-3-hydroxybutyrate can also act as competitive inhibitors to ketone body transport. Since ketone body transport across the blood brain barrier is a limiting factor to ketone body utilization in brain every effort should be made to keep the blood concentration of these unphysiological enantiomers at low levels during ketogenic therapy. When blood ketone body concentrations are elevated to levels found in starvation, heart, muscle, kidney and brain utilize ketone bodies as the preferred energy substrate.” from US2001/0014696A1, patent, RL Veech.
Rob Coberly
February 28, 2016 at 8:39 pm
Concerning specific DBHB, or racemic mixtures. There are a few references. Anyone who has more, please chime in.
References to L-beta hydroxybutyrate are not common. Even the classic 1980 Robinson and Williamson “substrates and signals” review of ketone bodies expressed uncertainty about any metabolic role for the L isomer. That paper does note that, “…The presently known pathway of utilization of the L(+)-isomer is different from that of D( -)-3-hydroxybutyrate since 3-hydroxybutyrate dehydrogenase is specific for the D-(-)-isomer…and there is no evidence for the existence of either a mitochondrial L-3-hydroxybutyrate dehydrogenase or a racemase catalyzing the interconversion of L( +) and D( -)-3-hydroxybutyrate…” So observations about D BHB are not likely to just carry over to L BHB. One of the important enzymes leading into metabolism is specific for the D isomer only.
Importantly, from “D-beta-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease”, Serge Przedborski et al, The Journal of Clinical Investigation, September 2003, Volume 112, Number 6 – excerpts.
“…Circulating DbetaHB readily crosses the blood-brain barrier and enters mitochondria, where it is metabolized by beta-hydroxy-butyrate dehydrogenase to acetoacetate; the latter is converted to acetyl-CoA, which feeds into the Krebs cycle…To control for the specificity of DbetaHB neuroprotection, another set of MPTP-injected mice received infusion of the inactive isomer LbetaHB. In these mice, the loss of dopaminergic neurons was as severe as in mice infused with vehicle…Thus, DbetaHB, but not its inactive isomer, can attenuate neurotoxic effects of MPTP on dopaminergic cell bodies in the (substantia nigra pars compacta) and nerve fibers in the striatum…Consistent with DbetaHB being a mitochondrial substrate, we found that it increased oxygen consumption in a dose-dependent manner…The effects of DbetaHB in supporting mitochondrial respiration are stereospecific, since the inactive isomer LbetaHB failed to improve oxidative phosphorylation…As shown in Table 3, DbetaHB increased ATP production from a base line of 5.37 ± 0.30 nmol/mg protein to 76.16 ± 6.11 nmol/mg protein. The increase of ATP production was not detected with the inactive isomer L`HB (3.85 ± 0.24 nmol/mg protein)…”
That is, L BHB and D BHB were both studied, in living mice and in brain mitochondrial preparations from those mice; the L isomer did not support oxidative phosphorylation and did not provide neuroprotection from mitochondrial toxins. The ATP content measured (their table 3) showed cells given L BHB had a lower content than with no substrate at all.
It will be more expensive to obtain stereospecific D BHB, but it is most likely to be worth it. I am concerned that inactive L BHB may compete with D BHB for blood brain barrier transport, or cell or mitochondria entry. I wonder if that has been looked at.
keith
March 22, 2016 at 9:18 pm
I don’t agree with the line about getting the benefits without the dangers of a high fat diet. When following a ketogenic diet your body uses fats differently than when eating the same fats on a carb based diet. For example on a ketogenic diet the blood levels of saturated fat is lower (what really matters) even when consumption of these saturated fats has increased.
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Mayumi Liwayway Espina
January 7, 2019 at 5:50 pm
This is a very interesting article. Just like everything, this needs a lot of studying. This could either turn into a great success or a big failure. Ketogenic diet is on the loop right now and a lot of people are getting hooked. Thanks for sharing this.