One of the earliest studies looking at the effects of ketones, entitled “The Metabolism of Bovine Epididymal Spermatozoa,” was published in the Archives of Biochemistry in 1945 by H. A. Lardy, R. G. Hansen, and P. H. Phillips. They looked at the effects of sixteen different substances that might be used as fuel by cow sperm, including various sugars, lipids, and other metabolites. They found that the ketone bodies beta-hydroxybutyrate and acetoacetate were unique among these sixteen substances in that they increased the motility of the sperm while at the same time reducing the amount of oxygen consumed to accomplish this. Fifty years later, Dr. Richard Veech and his associates at the NIH were able to work out how this happens.
After Dr. Veech received his degree in medicine and completed a one-year research fellowship at Harvard University, he had a two-year research fellowship at the NIH. In 1966, he went to Oxford University to work in the lab of the Nobel Prize–winning physician and biochemist/researcher Hans Krebs of “Krebs cycle” fame. For more than three years, he honed his skills there as a biochemist, working out details of certain chemical reactions that occur within mitochondria, among other things. Dr. Veech has told me that this work is so complex that most humans cannot begin to understand it. After Dr. Veech left Oxford, Dr. Krebs visited his lab at the NIH to review past studies and future projects every year until he died in 1981.
In a paper written by Dr. Veech in 2006 for the “Mini Series: Paths to Discovery” in Biochemistry and Molecular Biology Education, he relates how he came to study the effects of ketones:
By the mid-1980s, review processes at NIH became more bureaucratized and centralized by NIH administrators along the lines of the ‘peer-reviewed’ process in which ‘experts,’ usually grantees of the institute under review, reviewed the intramural NIH laboratories. The work of our lab went from being a “national treasure” to a “waste of money,” depending upon the eye of the beholder. By 1991, the work of the laboratory at NIH was judged to be inadequate, and I was notified that the laboratory would be shut down in two years’ time. I decided that I would spend the last available two years studying a subject that I thought would be important and to take no notice whatever of programmatic goals set by administrators without actual laboratory experience. To their great credit, the laboratory members, who were all to be terminated at the end of this period, accepted my explanation that this was a “Birkenhead drill” [defined as “courage in the face of hopeless circumstances”] and stayed at their posts, completing the work outlined during the remaining two years.
The problem chosen was to determine the effects of changes caused by the ketone bodies (beta-hydroxybutyrate and acetoacetate), insulin, and their combination on the working perfused rat heart.
Dr. Veech and his associates proceeded to study ketone bodies intensely to learn more about what they do. The first article about their study of ketones, “Control of Glucose Utilization in Working Perfused Rat Heart,” appeared in the October 14, 1994, issue of the Journal of Biological Chemistry. Glucose was the focus of this very complex study, specifically how the enzymes involved in glucose metabolism in the working rat heart are affected by various substrates, one of which was the addition of ketone.
The second paper, entitled “Insulin, Ketone Bodies, and Mitochondrial Energy Transduction,” was published in the FASEB Journal in May 1995. The study involved perfusing working rat hearts with a solution containing glucose. To this solution they added insulin, or the ketones beta-hydroxybutyrate and acetoacetate, or a combination of insulin and the ketone-body mixture. The ketone levels were consistent with those that occur during starvation. They found that the addition of either insulin or ketone bodies increased the efficiency of the hearts by about 25 percent, and the combination of insulin and ketone bodies increased the efficiency by about 36 percent. The hearts pumped harder using less oxygen. They learned that ketone bodies were able to duplicate nearly all the acute effects of insulin.
The effects of insulin or ketones on the ability of the heart to work more efficiently is the result of increased production within the mitochondria of acetyl-CoA, the coenzyme from which the energy molecule ATP is made. This increased production of acetyl-CoA results in the generation of more ATP. The researchers were able to work out the biochemical details of exactly how this occurs. Ketones actually cause a sixteenfold increase in the production of acetyl CoA, similar to the effect of insulin. These findings indicate that during starvation, when glucose is not readily available and insulin levels are low, ketones can substitute for both glucose and insulin to ensure that cells continue to survive and function normally.
Ketones do not require insulin to enter the cell. Instead, ketones require a monocarboxylate transporter to cross the cell membrane. Ketones bypass several steps in the process normally used by glucose to enter the mitochondria and start the process of making acetyl-CoA and eventually ATP. This is particularly important in the brain, since insulin cannot cross the blood/brain barrier. For example, in the brains of people with Alzheimer’s, which have become deficient in insulin and resistant to insulin, ketones can provide an alternative source of fuel. Ketones can also carry out many of the effects that are carried out by insulin in the normal, healthy brain. Ketones can even stimulate the production of glycogen, the stored form of glucose, a function normally provided by insulin.
Dr. Veech learned that by increasing the efficiency of ATP, ketones have the added benefit of increasing the efficiency of how cells use sodium, potassium, and calcium, the three major electrolytes in our bodies. These electrolytes are very important to the transport of substances into and out of the cell. Sodium, potassium, and calcium must be maintained within very specific ranges both inside and outside the cell, or there will be dire consequences. For example, when a brain cell is injured, let’s say by trauma to the head, potassium leaks out of the cell and too much sodium and calcium enter the cell. This causes the cell to swell and lose its ability to function normally. Ketones prevent or correct this problem of electrolyte imbalance by increasing ATP. Thus, injuries to the brain by direct trauma or lack of oxygen could be treated by administering ketones.
One can envision that an intravenous solution containing ketones could be given immediately to an injured soldier, an accident victim, or a newborn who has suffered a lack of oxygen during delivery to reduce damage to the brain and other organs. (Successful studies of this will be discussed later in the chapter.) Dr. Veech has proposed in one of his ketone hypothesis papers from 2003 (discussed later) that the ketogenic diet might reduce seizures in people with epilepsy through the effect of ketones on ATP and the major electrolytes.
Dr. Veech has also found that ketones are able to reduce the amount of damage from free radicals within the tiny energy-generating mitochondria by their action on coenzyme Q10 (also called CoQ10). Coenzyme Q10 is another important coenzyme required for making ATP and also acts as an antioxidant. Ketones can also decrease damage to the cell by reducing the amount of hydrogen peroxide in the cytoplasm (the fluid within the cell). The antioxidants in fruits and vegetables that we hear so much about are other examples of substances that can reduce damage from oxygen free radicals.
In the discussion section of his 1995 paper, Dr. Veech states: “Provision of acetyl moieties within mitochondria has been suggested to reverse many age-related defects in mitochondrial ATP synthesis. Use of ketones may therefore provide unexpected benefits in the treatment of elderly patients or others suffering from oxidative damage to mitochondria.” He also states in the abstract summary: “… the moderate ketosis characteristic of prolonged fasting or type 2 diabetes appears to be an elegant compensation for the defects in mitochondrial energy transduction associated with acute insulin deficiency or mitochondrial senescence.” Simply put, raising the levels of ketones could be beneficial to people with diseases that involve a problem with damaged or aging mitochondria.
By the time this work was published in 1995, Dr. Veech states in his 2006 paper:
My lab had been closed, and its workers and techniques had been dispersed. As an over-age civil servant, I could not be “fired” but had no other visible means of support. I used this sabbatical in the closet to reflect on the implications of our findings on the remarkable effects of ketone bodies on mitochondrial redox potentials. Ketosis, resulting from either prolonged fasting or feeding a high fat, low-carbohydrate diet, has been used to treat refractory epilepsy for over 100 years. An in-depth understanding of the biochemical details of the mechanism of action of ketone metabolism led to other and more widespread potential applications. What emerged from a detailed biochemical analysis of the effects of ketone metabolism was a surprising array of disease phenotypes, including specific rare monogenetic diseases and common polygenic diseases that might be benefited by mild ketosis…. Fortunately for my research, other sources of non-traditional funding became available that allowed us the chance to determine whether our hypotheses about the therapeutic benefit of alteration in metabolic substrates in a number of disease phenotypes were true. If these hypotheses prove to be correct, it will be ironic that the funding was provided by the Department of Defense, not the Department of Health and Human Services. Little did I know in 1966, when Krebs assigned me the task of determining the redox state of the NADP (nicotinamide adenine dinucelotide phosphate) system, that I would still be working on the problem forty years later. What a ride!
Thus, interest in his work with ketones and subsequent funding on the part of the Department of Defense allowed Dr. Veech to continue this research in his laboratory at the NIH.
In 1997, Dr. Veech, Dr. Yoshihiro Kashiwaya, and Todd King published another paper in the American Journal of Cardiology, further elaborating on the effects of ketones and their similarity to the actions of insulin in their effects on the working rat heart. In the summary, he states, “The ability of a physiologic ratio of ketones bodies to correct most of the metabolic defects of acute insulin deficiency suggests therapeutic roles for these natural substrates during periods of impaired cardiac performance and in insulin-resistant states.”
The week before the paper was published, Dr. Veech filed a patent application simply entitled “Therapeutic Compositions” that enabled him to produce a form of the naturally occurring ketone body beta-hydroxybutyrate. The patent application has been regularly updated since then. The opening summary states:
Compositions comprising ketone bodies and/or their metabolic precursors are provided that are suitable for administration to humans and animals and which have the properties of, inter alia, (i) increasing cardiac efficiency, particularly efficiency in use of glucose; (ii) for providing energy source, particularly in diabetes and insulin-resistant states; and (iii) treating disorders caused by damage to brain cells, particularly by retarding or preventing brain damage in memory associated brain areas such as found in Alzheimer’s disease and similar conditions. These compositions may be taken as nutritional aids, for example by athletes, or for the treatment of medical conditions, particularly those associated with poor cardiac efficiency, insulin resistance and neuronal damage. The invention further provides methods of treatment and novel esters and polymers for inclusion in the composition of the invention.
For many conditions, this ketone ester could be taken as a food that is capable of achieving levels of ketones that occur during starvation and on the classic ketogenic diet. At such levels, the ketone ester should be well tolerated and not result in untoward complications. In addition, the compound could be given intravenously to people with traumatic brain injury or who lack oxygen and who would not be able to take the substance by mouth.
While developing the ketone ester, Dr. Veech has continued to research the effects of ketones. As a result of his findings on the heart, it occurred to Dr. Veech that ketones might protect neurons in Parkinson’s and Alzheimer’s diseases. To prove this hypothesis, neurons were taken from the areas of the brain associated with both diseases and grown separately in culture. The cells were subjected to a substance known to cause these diseases. The ketone body beta-hydroxybutyrate was added to some of the cell cultures at levels found during starvation. The researchers found that addition of the ketones significantly increased the survival of the neurons. In addition, researchers found that the size of the cells was larger and had a greater outgrowth of neurites (axons and dendrites that connect neurons with other cells), suggesting that ketones can act as growth factors to neurons in culture.
Therefore, not only do ketones protect the neurons by providing more energy within the mitochondria, but they also appear to increase the growth and development of neurons. In the conclusion of his report on this study, “D-Beta-Hydroxybutyrate Protects Neurons in Models of Alzheimer’s and Parkinson’s Disease,” published in the May 9, 2000, issue of the Proceedings of the National Academy of Sciences, Dr. Veech states:
… elevation of ketones may offer neuroprotection in the treatment or prevention of both Alzheimer’s disease, where therapy is lacking, and Parkinson’s disease where therapy with L-dopa is time limited. The high-fat diet used in childhood epilepsy may not be suitable because of its atherogenic [arterial plaque-forming] potential; however, alternative dietary sources of ketones produced biotechnologically may overcome this difficulty and provide benefit without the undesirable effects of current ketogenic diets.
Dr. Veech’s three important papers regarding the potential use of ketones to treat and prevent disease followed in 2001 and 2003.
• The first paper, entitled “Ketone Bodies, Potential Therapeutic Uses,” appeared in the International Union of Biochemistry and Molecular Biology (IUBMB) Life in 2001 and was co-authored with Britton Chance, Yoshihiro Kashiwaya, Henry A. Lardy, and George F. Cahill Jr., the physician who discovered that neurons can use ketones as an alternative fuel to glucose.
• A second paper entitled “Ketoacids? Good Medicine?” was published in 2003 following a presentation by Dr. Cahill for the American Clinical and Climatological Association, and was co-written by Dr. Veech. This paper emphasized the importance of ketones in the evolution of humans with our large brain relative to other creatures.
• A third paper published in 2004, “The Therapeutic Implications of Ketone Bodies: The Effects of Ketone Bodies in Pathological Conditions,” written solely by Dr. Veech for Prostaglandins, Leuko trienes and Essential Fatty Acids, explains the metabolic effects of ketones in exquisite detail: how ketones function as a fuel in the cell and in mitochondria and how they actually provide a more potent fuel than glucose; how ketones replace insulin during starvation, carrying out the same effects but in a more primitive way; and how ketones reduce oxygen free radical damage.
Another important paper, “Ketones: Metabolism’s Ugly Duckling,” mentioned in Chapter 16, which appeared in the October 2003 Nutrition Reviews, was written by Dr. Theodore VanItallie, longtime colleague of Dr. Veech, along with Thomas H. Nufert. Dr. VanItallie was involved in the early work with medium-chain triglycerides, confirming that these fatty acids are partly converted in the liver to ketones. He also found that the classic ketogenic diet appears to be beneficial to people with Parkinson’s disease. The article provides an elegant discussion of how ketones work, along with the basis for treatment with ketones of certain neurodegenerative diseases, with an emphasis on Alz heimer’s and Parkinson’s diseases.
One of the most exciting studies I have read about potential reversal of neurodegenerative disease by ketones was published in April 2003 in the Lancet entitled “D, L-3-Hydroxybutyrate Treatment of Multiple Acyl-Coa Dehydrogenase Deficiency.” Johan Van Hove, M.D, Ph.D., and his associates reported successful treatment of three young children with a sodium salt of the ketone body beta-hydroxybutyrate. The three children each had a very rare enzyme defect called multiple acyl-CoA dehydrogenase deficiency (MADD). People with this defect are unable to use fat to produce energy once they have used up their stores of glucose. One of the three was paralyzed and near death at two years of age and had a nearly complete reversal to walking and talking nineteen months after beginning treatment with ketones. Similar improvements occurred in the other two children who were treated with the ketone compound. This study provided important evidence that ketones can be used to treat a life-threatening disease and even reverse the effects of this disease without side effects. It is important to note that while some improvements occurred during the first days, other improvements occurred over many months. Another exciting point is that the levels of ketones reached in this study are relatively low—0.3 millemoles per liter (mmol/l)—similar to the levels we measured in Steve after consuming coconut oil and MCT oil.
In summary, as stated in Dr. Veech’s patent application to make the ketone ester (World Intellectual Property Organization/1998/041200), ketones could be used to treat disease by:
• Acting as a substitute for insulin in conditions such as insulin deficiency and insulin deficiency, where the normal insulin signaling path is disordered. (Alzheimer’s, also called diabetes type 3, is one disease process that would benefit from such treatment.)
• Bypassing the block in the use of glucose by the brain that occurs in Alzheimer’s disease and many other conditions and providing an alternative source of energy to the brain, thereby preventing cell death. (This slows the progress of memory loss and dementia.)
• Increasing energy production in certain types of heart failure in which part of the problem is the inability of heart muscle cells to produce enough energy to function normally. (Ketones have been found to increase the efficiency of the heart by 25 percent, while reducing the amount of oxygen required in the process.)
• Increasing the supply of acetylcholine in the brain of people with Alzheimer’s by increasing acetyl-CoA in the mitochondria. (Drugs such as Aricept and Exelon work to increase acetylcholine by blocking the enzymes that break it down rather than increasing the amount of acetylcholine made by the brain.)
• Increasing blood flow to the brain.
• Decreasing cerebral edema (swelling in the brain) and improving brain function after lack of oxygen, injury to the brain, or lack of blood flow to an area of the brain.
• Increasing cell survival, improving cell function, and encouraging growth of new cells and connections between cells.
• Stimulating the production of nerve growth factors and other substances that may result in the growth of neurons and nerves and also improve how well they function.
Dr. Veech also suggests that the ketone ester could be started as soon as a predisposition to Alzheimer’s disease is determined, such as when a person is found to have a gene mutation known to carry a high risk of Alzheimer’s.
Because of their properties, ketones could be used to treat a number of diseases in addition to Alzheimer’s.
Currently, an estimated 5.3 million people in the United States suffer from Alzheimer’s disease at a cost of $148 billion per year. Treatments with medications that increase certain brain chemicals do not cure the disease but appear to slow its progress. Billions of dollars have been invested worldwide to learn the exact cause of this disease, with the expectation of finding a cure, but the answer has eluded researchers. Unless a means of preventing and treating this disease becomes available, as the Baby Boomers age, a projected 15 million people in the United States will have this horrific disease by the year 2050. The ketone ester of beta-hydroxybutyrate could be the light at the end of the tunnel.
In summary, a major hallmark of Alzheimer’s disease is progressive insulin deficiency and insulin resistance in the brain. Ketones can be used by all brain cells as an alternative fuel to glucose and therefore could allow insulin-resistant brain cells to function more normally and survive. Ketones actually bypass several of the steps needed to use glucose as a fuel, entering directly into the chemical chain of events that leads to making acetyl-CoA and then ATP. In addition, ketones have many of the same effects as insulin in the brain. Ketones can provide fuel to the mitochondria, which then increase the production of the various metabolites needed to make ATP. In addition, ketone bodies can reduce damage to the mitochondria from free radicals.
It is possible, with the introduction of ketones in the body, that some repair and reversal could occur in Alzheimer’s disease, since ketone bodies were shown in Dr. Veech’s 2000 PNAS paper to increase the neurite outgrowths in hippocampal cells exposed to ketones. It seems likely that ketones can stimulate the growth and survival of neurons as well as the extensions from neurons (axons and dendrites), thereby increasing the connections between brain cells (synapses). The decrease in synaptic density is likely the primary pathological defect in Alzheimer’s disease.
The ester of the ketone body beta-hydroxybutyrate, if used by people who are at risk, could potentially prevent Alzheimer’s disease. In addition, for people who already have the disease, this ketone ester could potentially halt the progress of the disease and perhaps even reverse some of the damage that has already occurred. Like insulin for the person with type 1 diabetes, the ketone ester could provide an effective treatment—a cure—for Alzheimer’s disease.
The patent application for the ketone ester lists a number of other less common and rare dementias that could potentially respond to treatment with ketone bodies, including:
• Bovine spongiform encephalopathy (BSE, or “mad cow disease”)
• Corticobasal degeneration
• Creutzfeldt-Jakob Disease (CJD)
• Dementia associated with Pick’s disease
• Dementia of Parkinson’s with frontal atrophy
• Down syndrome associated Alzheimer’s
• Frontal temporal lobe
• Lewy body dementia
• Posterior cortical atrophy (PCA)
• Progressive supranuclear palsy
• Vascular dementia
In addition, I know of one person with PCA who had a dramatic improvement after consuming oils with medium-chain triglycerides and has continued to show benefit nearly two years later.
About 500,000 people in the United States suffer from Parkinson’s disease, another progressive neurodegenerative disease that is classified as a movement disorder. People with this disease gradually develop slowness of movement (bradykinesia), become stiff, and develop tremors. About 30 percent of people with Parkinson’s eventually develop dementia. In Parkinson’s, neurons that make a substance called dopamine are affected in a part of the brain called the substantia nigra. Dopamine acts as a hormone and as a neuro-transmitter, a chemical that allows neurons to communicate at the synapses. Dopamine plays an important role in behavior and cognition, voluntary movement, sleep, mood, attention, working memory, and learning.
Like Alzheimer’s, the disease process in Parkinson’s involves dysfunction of mitochondria. The exact cause of this dysfunction is unknown in most cases, but it is thought to be related to damage from oxygen free radicals. The neurons that produce dopamine contain a high iron content, which makes them particularly susceptible to this type of damage. Similar to Alzheimer’s, there is decreased glucose uptake on FDG-PET scans in the affected area of the brain.
Dopamine cannot cross the blood/brain barrier, but its precursor L-dopa can. So people with Parkinson’s can obtain some relief by taking L-dopa. As the disease progresses, these neurons die, and eventually this treatment no longer works or the side effects begin to outweigh the benefits.
The ketogenic diet has been shown to help people with Parkinson’s. In 2005, Dr. Theodore VanItallie reported results of a feasibility study in which he tested a hyperketogenic diet on seven volunteers who had idiopathic (cause unknown) Parkinson’s (VanItallie, 2005). A test called the Unified Parkinson’s Disease Rating Scale (UPDRS) was administered before and at the end of the study. The five people who completed the twenty-eight-day study had improvements ranging from 21 to 81 percent on the UPDRS, for an average improvement of 43.4 percent.
The ketone ester could provide treatment for Parkinson’s disease by reducing free radical damage to the very important dopamine-producing neurons. Ketones could provide energy to malfunctioning mitochondria. Also, in one of Dr. Veech’s studies, ketone bodies prevented death in neurons that were subjected to a substance that causes Parkinson’s disease.
In addition to Alzheimer’s disease, sometimes called type 3 diabetes, many other diseases involve a deficiency of insulin and/or insulin resistance. Ketones can act as an alternative fuel for all tissues with the exception of the liver and could prevent progressive damage to multiple organs over time.
In addition to Alzheimer’s disease, here are some examples of insulin-deficient and insulin-resistant conditions that could benefit from treatment with ketones:
• Alcohol abuse
• Chronic stress
• Conditions requiring steroid use
• Cushing’s disease
• Diabetes mellitus types 1 and type 2
• Diseases with chronic inflammation
• Leprechaunism, also called Donohue syndrome (rare genetic mutation that affects insulin receptors)
• Metabolic syndrome (abdominal obesity, elevated cholesterol, and high blood pressure)
• Polycystic ovarian syndrome
• Prediabetes (insulin resistance)
• Rabson-Mendenhall syndrome (rare genetic mutation that affects insulin receptors)
A number of other conditions share this problem of decreased glucose uptake as demonstrated by abnormal PET scans and could benefit from treatment with ketone ester:
• Age-related memory impairment
• Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease)
• Birth asphyxia
• Cushing’s disease
• Huntington’s disease (also called Huntington’s chorea)
• Mild cognitive impairment (precursor to Alzheimer’s)
• Multiple sclerosis
• Some types of autism (many children respond to gluten-free or carbohydrate-specific diet)
• Stroke
• Sudden lack of oxygen
• Traumatic brain injury
Some rare genetic defects involving a block in glucose transport into cells or in metabolism of glucose could benefit from treatment with the ketone ester:
• GLUT-1 deficiency syndrome (currently treated with the ketogenic diet) and other glucose transporter diseases
• Glycogen storage diseases
• Leigh’s syndrome
Diseases that involve mitochondrial dysfunction could also respond to this treatment:
• Friedreich’s ataxia
• Mitochondrial myopathies
• Multiple sclerosis
• Muscular dystrophy
• Myasthenia gravis
• Diseases involving mitochondria in other organs
• Multiple acyl-CoA dehydrogenase deficiency (MADD)
The classic ketogenic diet and several modifications of it have been used successfully for nearly 100 years to eliminate or reduce the frequency of epileptic seizures in children and some adults who do not respond to treatment with anticonvulsants. When the diet is rigidly adhered to, the levels of ketone bodies are in the 2 to 5 micromoles per liter (mmol/l) range, comparable to those in starvation. However, a single deviation in the diet, such as consuming too many carbohydrates for a single meal, can suddenly reduce the level of ketones and cause seizures to reoccur. Currently, it is not known with certainty whether it is the high level of ketones and/or the extremely low level of carbohydrate in the diet that is responsible for controlling seizures. If the high level of ketone bodies is the primary factor in controlling seizures, then treatment with the ketone ester to maintain these high levels could replace the ketogenic diet, a big relief for many families dealing with this disease.
Until the ketone ester is available, incorporating MCT oil into the ketogenic diet could make the process somewhat easier.
• Diabetes mellitus types 1 and 2 (Even though high blood sugar is the hallmark of these diseases, diabetics are prone to attacks of low blood sugar if too much insulin is available in relation to how much sugar is consumed; this can occur, for example, by overestimating how much insulin is needed).
• Hypoglycemia of the newborn (affects about 10 percent of newborns)
• Infant of diabetic mother syndrome
• Russell Silver syndrome
The eye is an extension of the brain, and certain eye diseases are the result of degeneration of the highly specialized neurons in the optic nerve or in the retina. It is then conceivable that providing circulating ketone bodies could bring about improvement in these conditions, including certain forms of:
• Glaucoma
• Optic atrophy
• Optic neuropathy
The above lists are far from inclusive of all the diseases and conditions that could benefit from treatment with ketones. Any disease should be considered for treatment with ketones that involves insulin resistance, decreased glucose transport into neurons or other cells, abnormal release of glycogen from cells resulting in hypoglycemia, and/or mitochondrial dysfunction, as well as certain rare genetic defects. For instance, the ketogenic diet has been shown to be beneficial for people with certain types of cancerous tumors, which use only glucose for energy and cannot use ketones. Several studies in animals and in humans show that elevation of ketone levels through the ketogenic diet can cause astrocytomic tumors in the brain to shrink, by as much as 80 percent in a mouse study (Seyfried, 2005).
It is very important that such treatment is discussed with the person’s physician to determine if it is justified and would not be harmful or possibly worsen the disease.
Since the mid-1990s, Dr. Veech and his associates have worked tirelessly at the NIH to study ketone bodies and to find the chemical formulation of the ketone ester that will produce results. About three years ago, he hit upon a successful formulation of the ketone ester. He and his associates have been making this, day in and day out, producing about nine to ten pounds per week. Because certain components needed to make the ester are quite expensive, Dr. Veech has been working on methods to produce the ester inexpensively. He is now very close to meeting the goal of making the ketone ester affordable so that everyone who needs it will be able to get it.
However, the amount that can be produced in his lab would provide enough ketone for only four or five people on an ongoing basis. Thus, a much larger facility is needed to mass-produce the ketone ester. This, of course, requires considerable funding. Dr. Veech has suggested that a viable option would be to convert one of the bankrupt ethanol plants to make the ketone ester, which involves a similar process. There are many of these plants across the country.
In the summer of 2009, about fifty normal, healthy adults were recruited to participate for several months in toxicity testing of the ketone ester. The dosage was gradually increased until levels were achieved in the range that occurs with starvation and the classic ketogenic diet. There were no adverse effects. Dr. Veech and his associates launched a pilot study of people with Parkinson’s disease in Oxford, England. He explains that within twenty-eight days it should be apparent whether a person with Parkinson’s responds to the ketone ester or not, whereas studies involving Alzheimer’s typically require a year or longer to determine if a compound is effective, due to the nature of the disease process. A study of the effects of ketone esters on physiological and cognitive performance in normal subjects and elite athletes is now underway at Oxford University under the direction of Dr. Veech’s longtime collaborator, Professor Keiran Clark.
At this point, those of us who have loved ones with Alzheimer’s can encourage the people who make funding decisions to consider the potential of the ketone ester and provide the moneys needed to begin the study of ketone esters in people with Alzheimer’s disease as well. After all, we and our loved ones are running out of time.