Travis Christofferson M.S. Dominic D’Agostino Ph.D.
Be sure to check out Part 1, and Part 2.
“Wait a Minute, This Didn’t Have to Happen”
As the Abrahamses flew to Baltimore for the last remaining chance to treat Charlie’s unremitting seizures, their thoughts cartwheeled between sadness, desperation, and the last sliver of hope. Most likely they were experiencing the same emotions as the Howlands as they rode the train toward Battle Creek eighty years earlier. As he traversed the American landscape, Abrahams was entirely unaware of the rich history surrounding the ketogenic diet as a treatment for epilepsy. That it was once the standard-of-care for epilepsy would have shocked and bewildered him even more so. For Abrahams, and most doctors and patients across the country, the ketogenic diet was dead – reduced to the equivalent of an herbalist working out of a strip mall.
When they arrived at Johns Hopkins they met with Dr. Freeman and his dietitian, Millicent Kelly. The pair seemed perfectly matched. Dr. Freeman was the maverick. “He was larger than life; fearless; he knew he was considered an outlier by a lot of his colleagues, but in a way I think that intrigued him.” Millicent was the soft side – comforting, Grandmother-like mannerisms that were amplified to almost cartoonish levels. With a charming and soothing voice that seemed to round the edges of every word, she explained the diet to Abrahams. With no time to spare, they began the diet with a jump start, they fasted Charlie the rest of the day and into the next.
By the next day, when Abrahams held his son he could already tell a difference; he just felt “less intense”, like something had been turned down. By the next day, forty-eight hours later, something remarkable happened: his son stopped having seizures. Completely. The Abrahamses returned home brimming with optimism and hope. Days passed, and then weeks, and the seizures remained at bay. The diet had an incredibly powerful impact. It had done what of drugs and surgery were unable to do; it had brought his son back from the abyss. Charlie began to thrive. His mental capacity and energy returned. The house, once filled with tears, was now filled with joy.
The story of the Abrahamses would have ended there – they would have been just one of the ten or so that Dr. Freeman and Millicent quietly helped every year. But like Howland before him, the experience aroused something deep. Medicine had failed them. Things begin to stir in Abrahams when he returned to his normal life. Something just didn’t sit well. “All of a sudden my eyes opened up in the middle of the night, and I said ‘wait a minute, this didn’t have to happen.’ Ninety percent of these seizures didn’t have to occur. Waking up around the clock, and pouring drugs down his throat, didn’t have to occur.” Abrahams’ epiphany morphed into puzzlement and anger. What motivated him the most is that he was in a position to prevent this from happening to others.
Where Howland had the money of a wealthy corporate lawyer, Abrahams had something even better – perhaps the best resource in the world for taking up a cause: Hollywood. Abrahams had produced blockbuster hits like Airplane, Naked Gun, and Hot Shots. If it was simply a lack of information, he could change that. So he and his wife Nancy started the now famous Charlie Foundation dedicated to disseminating information about the ketogenic diet so Charlie’s story would not be repeated. On October 26th, 1994, the NBC news program Dateline brought Charlie’s story into millions of living rooms across the country. At the end of the show viewers were given a number to call. Families that called were sent a video from the Charlie Foundation titled An Introduction to the Ketogenic Diet. The foundation also mailed the same tape to neurologists throughout the country. Shortly after, neurologists were mailed another video titled The Ketogenic Diet: Doctors Version. It was a well-orchestrated plan and its impact was enormous. Abrahams also had the Charlie foundation ready to fund a seven-center trial designed to measure the impact of the ketogenic diet once and for all. A trial would serve to demonstrate the efficacy of the forgotten diet for both patients and doctors.
It was timed perfectly. Shortly before the Dateline special the Charlie Foundation quietly had doctors, dietitians, nurses, and families with an epileptic child come to Johns Hopkins and receive intensive training on the use of the proven Johns Hopkins ketogenic diet protocol. The doctors and their staffs were then ready and waiting for the anticipated surge of new patients coming from media blitz that began with the prime-time Dateline special. As expected, the kids came from all corners of the country, desperate to try the new diet. Four years later Freeman published the results from 150 kids that entered the trial. The patient group enrolled in the trial was a tough lot. As a group, they averaged 410 seizures per month and had already failed to improve after trying an average of 6.2 medications. Nevertheless, the outcome was dramatic. Of the 55% still on the diet after a year, 27% were close to seizure free, 23% were significantly improved, and the remaining 5% had a less than 50% reduction of seizures. Three to six years later, 27% of these same children had few to no seizures and most were off of the diet and on fewer to no medication. To further raise public awareness, a year before the data from the trial was published, Abrahams released an ABC television movie titled First Do No Harm starring his good friend Meryl Streep. It was the dramatic portrayal of a Midwestern family’s struggle to find the ketogenic diet for their child with severe and unresponsive epilepsy. Eight million viewers watched the movie the night it was aired.
In truth, the Charlie Foundation’s clinical trial just confirmed the results of the thirteen other studies that had been performed since Wilder first purposed the diet as a treatment in 1921. The only difference this time, because of Jim Abrahams’ elegantly choreographed media campaign, people were paying attention. The study was presented at the annual American Epilepsy Society in 1996. Before the study was presented, the ketogenic diet was almost never mentioned at the annual gathering. But this time, combined with the media firestorm, it precipitated an avalanche of research the following year, and only grew in the years after that. The ketogenic diet had been resurrected – as quickly as it had fallen, because of the discovery of Dilantin, it had been revived by a passionate family and their sick child.
Seven minutes and fifty-five seconds into the Dateline special featuring Charlie’s story, Charlie’s doctor, Donald Shields, said something important. The reporter asked Dr. Shields: “You had some knowledge this diet was probably working back at Johns Hopkins (Dr. Shields and Dr. Freeman were actually good friends), yet you dissuaded the Abrahams from attempting it, how come?” Dr. Shields paused, looked at the ceiling, and said, “Well, because I don’t think we had exhausted all of the medical approaches yet. There were actually other medications we hadn’t tried yet.” Drawing a distinction between so called “medical approaches” and the ketogenic diet reveals volumes of the way many doctors view the dietary protocol – something existing outside of the realm of real medicine – something strange, nonconventional, and alternative. Why else would the diet have faded into complete obscurity in the first place?
Even today the diet is rarely used as a first line treatment. It is still something held in reserve. Epilepsy is almost always treated first with drugs. Medication will make half of the patient’s seizure free for an extended period of time. But if a patient doesn’t respond to the first drug the odds rapidly diminish. In these cases a second drug will only make an additional 14% seizure free. If that drug fails then the likelihood of seizure control using drugs falls to about 1 to 2 percent. Remarkably, even with the most recent anti-seizure drugs, these ratios have remained essentially the same throughout the century– as if some fundamental barrier cannot be breached by drugs alone. So that leaves more than 30% of epileptic patients without seizure control even with the latest, and best medications. Before Abrahams pulled the diet from obscurity, these patients had nowhere to turn. Today, this is where the ketogenic diet is typically used – as an option of last resort. For the over 30% of patients with uncontrolled seizures after failing drug therapy the ketogenic diet is a godsend. If maintained properly, it renders half of this desperate group either completely or extremely close to seizure free. These incredible results have been shown consistently in study after study throughout the 20th century. In addition, most kids who use the diet can transition back to a normal western diet after two years, never need drugs again, and remain seizure free.
After combing through the statistics an inevitable question arises: why is the diet only held as an option of last resort? One can’t help but wonder: which is better as a first-line treatment, drugs, or the ketogenic diet? To be sure, the comparisons, from trials alone, are not apples to apples. A direct head to head comparison has never been done. The answer to this question remains unknown. However, there is a very important difference between the studies of anti-seizure drugs and the ketogenic diet: all of the modern studies of the ketogenic diet use a patient population that has failed drug treatment. The dietary trials have a built-in bias from the starting line. The tests done on the ketogenic diet are enrolled with the hardest cases – patients with gritty, embedded seizures that refuse to be blunted by the best medications available. “You’ve already peeled off the easiest cases. It’s like running a one-hundred yard dash with a weight chained to your leg,” said Dr. James Wheless, a pediatric neurologist, and a recognized expert on the use of the ketogenic diet. Even in the face of such difficult odds, the ketogenic diet shows incredible results.
Of course, any comparison of diet verses drugs must also include side effects. Even modern drugs aren’t completely benign. When Charlie was saturated in anti-seizure drugs Abrahams described him as a “zombie who lived in his car seat.” Although technology has continued to separate the sedative effect and the anti-seizure effect, it is not perfect. Drugs often leave patients lethargic, dizzy, and with double vision. Rashes appear, weight gain, abnormal liver function, kidney stones, and constipation. The biggest difference between anti-seizure medication and the ketogenic diet occurs in the brain. Indeed, the brain is ground zero in the debate of diet versus drugs. The side effects that occur from medication are not there in the diet, in fact, the opposite occurs. Doctors today notice the same mental effects as the original pioneers of the diet back at the beginning of the 20th century: increased alertness, improved behavior, reduced anxiety and depression. How the patient experiences life is markedly different between drugs and the diet – a variable that defies quantification.
The strict form of the diet is not without some issues. Side effects do occur, but they are very minor, including changes in lipid profiles, kidney stones, constipation, and a subtle slowing of growth. However, improvements in the diet formulation, macronutrient sources, supplements, and interventions have greatly diminished lipid abnormalities, constipation and kidney stones. A 2010 study at Johns Hopkins followed the outcomes of children treated with the ketogenic diet from 1993 to 2008 and found almost no long-term adverse effects. The only obvious effect was growth. Height was found to be reduced by 5 cm from the expected average. All other laboratory values were normal. Most importantly, the study found the subjects had continued to either maintain, or improve on seizure control, even into adulthood. Most of the families had few regrets and would recommend the diet to others. All added up – results combined with side-effects – many experts in the field give a nod to the ketogenic diet when directly compared to drugs. They feel the diet is often simply the best medical option. “No anticonvulsive drugs have that rate of beneficial effect,” wrote Dr. Freeman.
Despite the heroic efforts of Abrahams, his wife Nancy, and the Charlie Foundation, the ketogenic diet is still today underutilized. When an epileptic child enters a neurologist’s practice the typical scenario goes like this: the patient is prescribed a first-line drug. As stated above, this works about half of the time. For the half that fail to respond, the neurologist will prescribe another drug. This time the drug works in about one in seven kids (it doesn’t matter which drug is chosen, the statistics remain the same). For the kids that don’t respond to the second drug the neurologist will now almost always try a third. The chance the third drug will work now falls to one percent. This leaves over one in three kids that come back to the neurologist office in a desperate situation, after having failed three drugs. The neurologist now has a decision to make. According to a 2008 special report issued by a consortium of 26 world-recognized experts using the ketogenic diet from nine countries, this is precisely where the diet should be prescribed, after the failure of two to three drugs.
At this point the data begs to be heard: the ketogenic diet will make over half of this desperate group of kids either entirely, or very close to seizure free – the other half simply can’t or won’t maintain the diet for a variety of reasons – either they find the diet isn’t working, or it’s too hard to maintain. Prescribing a fourth drug has a vanishingly small chance of working. Yet, strangely, in many cases, the neurologist will keep going; writing script after script for more and more drugs – many never suggesting the diet – the same dreadful place Charlie and his family found themselves. When I asked Jim if Charlie’s “story” still happens today, he responded in a sober tone: “Sadly, Yes. And in many ways its worse; the reason is because there are more drugs. The physicians frequently say, ‘well there is another drug, let’s try that instead.’ From what we see, from those who contact us, I don’t know the exact statics, but rarely is the diet prescribed after the failure of two or three medications.” Why the diet continues to be marginalized is a poignant question. “It’s a culture shift,” said Dr. Wheless. “The mindset today is to take a pill and be done. If the diet was in pill form it would be the best treatment available.”
It raises an important question. Are we as a culture, both patients and physicians, willing to marginalize an incredibly effective therapy at the expense of some convenience? The question is especially relevant considering the price paid is so incredibly high. “One of the things that pisses me off the most is that the whole degree of difficulty thing; it’s not a medical question,” said Abrahams. “When you’re holding your kid while he has hundreds of seizures a day, and then you find out doctors aren’t giving you all the information…because they think, ‘it’s too difficult’ – where in medical school did they teach a course on what’s considered too difficult for the parents of a critically ill child.”
To get this right is not trivial. Epilepsy affects 65 million people across the globe – almost one percent of the world’s population. The most updated statistic released by the CDC claim 1 in 26 people will develop epilepsy at some point in their life. Despite extensive testing, over half of all cases are idiopathic, meaning no reason for the illness can be found. It mostly affects children, but can also affect adults – the chances increasing with age. It is a terrifying disease because there are so many unknowns. Still today, after centuries of investigation, researchers cannot tell you exactly what a seizure is, where it comes from, or why it stops. Words crop up like “multifactorial”, and “network effect”; which, although true, are really a way of saying “we don’t know exactly” – a bucket to throw very difficult problems in. Epilepsy erodes at the edges of life, interrupting, stealing, and isolating its victims. It is not passive. Over time, if severe enough, epilepsy won’t allow the brain to develop correctly. It is a tremendous burden for societies across the globe. And to let an extraordinary therapy remain under prescribed because of an undefined apathy is tragic and deserves an explanation.
Near the end of the Dateline special featuring Charlies story, the reporter asked Dr. Shields a final question: “Dr. Freeman tells us that fifty to seventy percent of the patients that come through his doors and get put on the ketogenic diet have success. Can you think of any drugs, in these hard cases, that have fifty to seventy percent success rates?” Dr. Shield’s again looked to the ceiling before answering, “Probably not anything that comes up to that level.” After some reflection, Dr. Shields backpedaled, and came up with a possible explanation for this astonishing situation – a reason why the diet is so often ignored. “There is no big drug company behind the ketogenic diet. And there will never be unless somebody starts marketing sausage and eggs with cream sauce on it as a drug.” Abrahams agrees with Dr. Shield’s assessment about why the diet remains in the shadows, “It’s not in the form of a pill, it can’t be administered with a scalpel, and the only people who profit from the ketogenic diet are the patients,” said Abrahams.
At the front-line of the Charlie Foundation’s efforts is their head nutritionist Beth Zupec-Kania. Over her 24 years with the Charlie Foundation Beth has trained dietitians in 10 countries and treated thousands of epileptic patients around the world. Perhaps more than anyone, she has witnessed the power of the ketogenic diet to treat epilepsy first hand. Typically, when she sees a patient they are on at least two anti-seizure drugs, have failed many more, are sick, frustrated, and exhausted. The patients that finally turn to the diet do so for more than one reason, said Zupec-Kania, “Their seizures continue unabated, or they are experiencing such severe side-effects that they are essentially nonfunctional, or both. Sadly, it’s usually both.” Most are left simmering in a state of pronounced lethargy because of the drugs.
Some drugs are worse than others. “The worst drug is Topamax”, said Zupec-Kania. “The nickname that the doctors call it behind the backs of patients is ‘Dope-a-max’ because it makes you feel so dopey. The patients can’t think of words that they used to know.” With the diet, she says that parents often notice a marked mental improvement once the child achieves ketosis. And this improvement occurs while the patients are on the same amount of drugs. Neurologists typically won’t start reducing the drugs until the patient has maintained the diet for at least a month; after it’s clear they are tolerating it well. The difference is striking. “All of a sudden the kid is paying attention, or stringing words together, kind of coming out of a fog,” said Zupec-Kania. “Jim has a video of this mom describing her six year old son: ‘he got up, he went to the bathroom, he cleaned up, and he came back to bed, and he hadn’t done that in the past year.’ The moment he went into ketosis he got his life back.”
Zupec-Kania said the short term side effects from the diet are preventable and researchers have yet to find any long term side effects. In fact, she has a different take. “I think these patients are healthier because of what they are not eating. Having worked with thousands of people, many of them will continue leaving processed foods and sugar out of their diets and are healthier in the long run,” she says. Through her quarter century of experience she has also made another striking observation. The ridged boundaries of the diet, the 4 to 1 ratio that has been the ‘gold standard’ for patients, may not be as vital to achieving seizure control as once thought. “Lots of patients probably don’t need the full blown ketogenic diet to get better; we could probably use something far more liberal and have the same effect. And I’m not even talking about the Modified Atkins Diet (which is used mainly for adolescents and adults with epilepsy), I’m talking about a paleo-type diet. I spoke to a mom last night who said her son just started having seizures out of the blue and after her nutritionist eliminated wheat and sugar from his diet his seizures stopped immediately. I would love to spare some people of the difficulty of the rigid form of the diet if it’s not needed. And now we’re finding just a low glycemic index diet can work in some cases. There is a whole spectrum of people and a whole spectrum of diets to meet their needs.
Dr. Jung Rho, of the University of Calgary is on the forefront of the current effort to answer Howland’s original question. For Rho, the question remains as haunting today as it did in 1921. Rho is nearing the end of a $2 million dollar, five year grant from the NIH to find the mechanism behind the ketogenic diet’s action on epilepsy. And as with those that came before him – Cobb, Lennox, Gamble, and Dr. Howland –the answer, wrote Rho, “remains elusive”. Rho’s estimation of the diet’s effect is essentially the same as Lennox’s “stones forming a mosaic” description almost a century ago: “At present, there are many hypotheses regarding KD (ketogenic diet) action, and while each is uniquely compelling, it is becoming more apparent that the KD likely works through multiple mechanisms,” wrote Rho. It’s not surprising Rho and others have yet to pin down the diet’s exact mechanism-of-action, given the nature of the human brain; an organ with 125 trillion neural synapses just in the cerebral cortex alone, a number roughly equal to the number of stars in 1,500 Milky Way galaxies. That level of staggering complexity, combined with the fact the pathophysiological mechanism behind seizures is still largely unknown, appears to have rendered Howland’s question still out of our technological reach. Perhaps the most important realization from Rho’s research is a deeper understanding of the nature of epilepsy: “The scientific literature involving the KD strongly supports the notion that epilepsy may indeed in part represent a “metabolic disease”, and that this concept could serve as a novel framework for the development of more effective anti-seizure drugs,” wrote Rho in July of 2015.
“The Genie is Out of the Bottle”
Even though, within the largely incentive driven arena of medicine, the ketogenic diet is still clearly under-prescribed today as a therapy for epilepsy, Jim Abrahams single-handedly managed to thrust the forgotten therapy back into the public and scientific consciousness. Before his Hollywood fueled campaign, the diet lie dormant – an artifact – after, researchers were once again stirred by the curious power of the ketogenic diet. Jim unknowingly resurrected a query from a by-gone era. To any curious biochemist, it is still astonishing in its own right that a simple shift in macromolecular consumption could have such a profound effect on brain chemistry.
By the late 1990’s, researchers turned their attention and laboratory space over to the ketogenic diet with revolutionary zeal. The number of researcher papers containing the phrase “ketogenic diet” exploded – from only two-hundred and twenty-five before the year 2000, to one-thousand four-hundred in the fifteen years after the year 2000. The earlier articles published were almost exclusively about the role of the diet in epilepsy, but around the turn of the century researchers had begun to nudge at the margins of the diet, exploring its possible role beyond epilepsy. Researchers, for the first time, began asking other questions of the diet: could it be used to treat or prevent other diseases?
First it was cancer in 1995. It was a tiny study – only two little girls with brain cancer – but the results hinted at a potent impact and precipitated an avalanche of research into ketosis and cancer. As biochemists uncovered the unique mechanistic-details of ketosis it opened new possibilities. One paper, in 2003, by NIH scientist Richard Veech and George Cahill, was a siren call. Specifically, it suggested the ketogenic diet, or ketone bodies by themselves, had the potential to affect a wide swath of pathologic conditions precipitated by insulin resistance and dysfunctional mitochondrial metabolism – fundamental processes that can lead to a constellation of problems. “What are the potential uses of beta-hydroxybutyrate in addition to pediatric epilepsy?” asked Veech, “Theoretically, any condition wherein oxygen supply to cells may be limited is an avenue for investigation. The list would encompass almost every disease state.” The paper was a foot in the door, behind which was an open-ended spectrum of possibility.
Other researchers took notice. Studies on physical performance, Alzheimer’s, and depression began in 2004. Parkinson’s disease, traumatic brain injury, type 2 diabetes, Lafora body disease, polycystic ovary syndrome (PCOS), and metabolic syndrome in 2005, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) in 2006, nonalcoholic fatty liver disease in 2007. Incredibly, perhaps counterintuitively, the ketogenic diet showed promise to “modify” the course of one disease after the next. The strangely vast spectrum of diseases the diet appeared to attenuate caught many researchers off guard. Clearly, the diet was able to shift metabolism and genetic expression at some base level that prevented, rejuvenated, and protected cells, tissues, and organs (notably the brain) from the accumulation of disease causing damage. Like epilepsy, in most cases the exact influence ketones were having on the variety of diseases remained elusive. Howland’s question became vastly expanded.
The Charlie Foundation became a conduit for the ketogenic diet’s sudden expansion in interest. The calls, once dominated by the pleas of epileptic patients, made an abrupt shift to other diseases. Now, around the turn of the century, when the phone rang, or an email came it, it was most likely a cancer patient, or someone with Alzheimer’s, or Parkinson’s, or other more obscure problems. The Foundation decided to evolve, and allowed itself to be led be the science. They changed their name from The Charlie Foundation for pediatric epilepsy to The Charlie Foundation for ketogenic therapies. Suddenly Zupec-Kania found herself teaching the diet to a vastly expanded group of health professionals. “We get more calls from cancer patients than epileptics now,” she said. Zupec-Kania has noticed the utility of the diet continues to heave and undulate, covering additional ailments; its circle of effectiveness, surprisingly, continues to expand. “I’m getting more and more calls from people with migraines which 16% of Americans suffer from. We’ve found out the diet is super effective for migraines. And surprisingly, the other one is hot flashes from menopause. The ketogenic diet, even a liberal ketogenic diet, cures hot flashes.”
For most of history epilepsy was viewed as a supernatural possession. Even today, vestiges of a mystical dimension linger. We know the disease is biological in origin, but it remains an enigma, it transcends our ability to succinctly explain it. That a subtle shift in energy metabolism is able to exorcise epileptic fits evokes imagery of preternatural healing; a biological force beyond our understanding. Incredibly, the discovery that the beneficial transition to ketone metabolism extends far past epilepsy, into unimaginable arenas of disease, only carries this image further – as evocative as it is astonishing. The literature reflects this feeling; words like “magical, superfuel, jet-fuel, and magic bullet,” slip from the pens of typically skeptical, objective and clinical scientists. The turn of the century marked the transition. The door is now open to a new era of medicine that, refreshingly, might have more to do with prevention than the never-ending cat and mouse game of diagnosing and treating disease after they have become intractably embedded – a game that is almost by definition, impossible to win. But it even goes beyond prevention. Ketone research has seduced us into imagining it might be possible to lift ourselves onto even higher planes of health and vitality. A bold new era of medicine beckons. Never have we asked if our health can be elevated, optimized, and extended with such vast technological resources at our fingertips.
The hybrid nature of human metabolism to utilize ketones as an energy source was not fully appreciated until the 1960’s. And even then it was typically confused with diabetic ketoacidosis – a pathological condition that has nothing to do with fasting or nutritional ketosis in general. Nevertheless the two were lumped together and the true disease modifying potential of nutritional ketosis was not fully appreciated until around the turn of the century. We now know, the shift to ketone metabolism goes far beyond the swapping of one fuel for another. Hidden just below the surface we’ve uncovered a new layer of complexity: we now know ketones are absolutely profound in their impact to human physiology. Critically, they act as signaling molecules and carry deeply conserved messages to our DNA – messages that vastly impact our overall health. Ketones change the architecture of our DNA, rearranging the way it is expressed, turning on the same rejuvenating pathways stimulated by caloric restriction or periodic fasting. Ketones appear to powerfully reduce inflammatory pathways – the smoldering process that is blamed for a vast spectrum of problems, even a reduction of overall lifespan. There is a growing consensus that most of the so called modern disease of civilization – obesity, type 2 diabetes, and Alzheimer’s (now called type 3 diabetes), cancer and many others – all ripple outward from a central core of metabolic dysfunction. These modern diseases, once considered pathologically distinct, converge to the same central place – a place that ketone metabolism concentrates its profoundly rejuvenating and repairing capacity. As Dr. Veech has said, “Ketosis is a normal physiological state. I would argue it is the normal state of man. It’s not normal to have a McDonald’s and a Delicatessen on every corner. It’s normal to starve.” Perhaps many of our modern ailments are a result of stepping too far from our natural state of existence.
It’s easy to recognize the societal resistance to any rigid dietary adjustment and the search is underway to find shortcuts. “The 20th century was about understanding the ketogenic diet,” said Dr. Wheless. “The 21st century is going to be about trying to capture its incredible benefits in a pill.”
Science is a building that is constantly under construction. The progress we are making today rises from a foundation built by others. In addition to all those mentioned in the article, the work of Drs. Richard Veech, Sami Hashim and Henri Brunengraber has laid the concrete that we in this field all work and build. These metabolic gurus were responsible for opening the blinds and illuminating the therapeutic potential of exogenous ketone supplementation.
Standing on the shoulders of these giants, our laboratory at University of South Florida has been studying the effects of ketone supplementation on numerous disease states, physical performance and resilience against extreme environments. Could these small molecules – once thought to be metabolic waste – hold the potential to treat and prevent a constellation of metabolic related illness? Do they capture the time honored benefits of caloric restriction or intermittent fasting? Can they enhance our health, vitality and longevity – allowing the baby boomers, a generation that refuses to “go gently into that good night”, to extract more from life for longer? The initial results look promising. The data emerging rapidly from studies on nutritional ketosis are compelling and have far reaching implications. Perhaps Jim Abrahams said it best: “The genie is out of the bottle.”
Links to relevant information:
Ellen Davis maintains a great site that’s been an excellent resource for many people.
This site has many of Dominic D’Agostino’s ketone publications downloadable for free.
A generally good site.
When it comes to understanding exogenous ketones, this post from Peter Attia is helpful to many.