Recent Ketogenic Therapy ConferencesMay 2018
By Ben Best
Carbohydrates and proteins are greatly reduced in a ketogenic diet, which requires the primary source of food energy to be fat and ketones derived from fat.
Carbohydrates are sugary foods or starchy foods such as bread, rice, or potatoes, which convert to blood glucose when digested.
For most of human history prior to the advent of agriculture, humans typically relied on fats and ketones rather than carbohydrates as a primary dietary energy source. Any excess energy (calories) ingested from food was converted into body fat.
Frequent food shortages, famine, and starvation resulted in stored body fat (and ketones from fat) being mobilized to meet cellular energy needs.
Agriculture made food availability more reliable, but agriculture resulted in grains (a form of carbohydrates) becoming the primary food source. Within the last century, carbohydrate consumption in the form of simple sugar has also skyrocketed.
In the 1920s, it was discovered that a ketogenic diet (low in carbohydrates and protein) could be used to treat epilepsy. But with the discovery of anti-epileptic drugs in the late 1930s, this form of epilepsy treatment became rare.
In the early 1990s, Charlie Abrahams, the young son of writer/director Jim Abrahams (best known for the film Airplane!) developed severe epilepsy. The boy was experiencing up to 100 seizures every day. Charlie received no benefit from surgery or drugs (from which he suffered unpleasant side effects). Against the advice of five expert pediatric neurologists, Abrahams started Charlie on a ketogenic diet. Charlie’s seizures stopped within days.
To make the benefits of the ketogenic diet more widely known, Abrahams made the movie …First do no Harm, starring Meryl Streep. The film portrayed an epileptic boy who, like Charlie, suffered from seizures and ineffective drug treatments. Abrahams also founded The Charlie Foundation (www.charliefoundation.org) to promote the ketogenic diet for epilepsy.
Since the 1990s, many scientists and physicians who are unafraid to challenge conventional medicine, along with a passionate community of self-experimenters, have discovered that a ketogenic diet can be used to treat obesity, diabetes, brain trauma, cancer, Alzheimer’s disease, Parkinson’s disease, autism, and many other conditions. The diet has become even more prominent than the Paleo diet, and conferences on the subject have become quite popular.
The following report is based on presentations I have heard at several ketogenic conferences in the past year.
Beth Zupec-Kania, RDN, is a former dietitian and nutritionist for The Charlie Foundation. Since the 1990s, she has been helping patients and their families to overcome challenges in implementing a ketogenic diet.
A ketogenic diet derives 80%-90% of calories from fat,1 which can be very unpalatable for many people. The diet is deficient in many vitamins and minerals, so supplements are required.2 Calcium and vitamin D are particularly important supplements,3 as well as vitamin B6 and magnesium.4 Oral citrate (potassium citrate) has been shown to reduce the risk of kidney stones on a ketogenic diet from 6.7% to 0.9%.5
L-carnitine is required for long-chain fatty acids to enter mitochondria. In some cases, a high-fat diet can deplete L-carnitine to the extent that high-plasma fats become a serious problem.6 Ms. Zupec-Kania recommends L-carnitine supplementation when this problem arises, but not otherwise.
Ms. Zupec-Kania cautions against the temptation to use artificial sweeteners in a ketogenic diet, because they have been shown to induce glucose intolerance by altering the microorganisms in the gut.7
Dr. Thomas Seyfried (professor at Boston College, Chestnut Hill, Massachusetts) does not accept the prevailing view that cancer is caused by DNA mutations in the cell nucleus.8 Instead, Dr. Seyfried believes that cancer is due to defects in the energy-producing mitochondria of cells, and that DNA mutations in the nucleus are a consequence of the defects in mitochondria.9
Defects in mitochondria could be due either to damaged mitochondrial DNA10,11 or due to damaged mitochondrial membrane components.12
Dr. Seyfried points to the fact that nearly all cancer cells are dependent on high rates of glucose utilization, regardless of the organ or tissue in which it originates.9
Although it is well-known that cancer tissue is heavily infiltrated by macrophages of the immune system, Dr. Seyfried believes that macrophage infiltration of cancerous tumors is not merely a symptom, but is the means by which cancers metastasize to different organs and tissues.13
Whether or not Dr. Seyfried is correct in his theories of the origin and spread of cancer, there is considerable evidence that a ketogenic diet can inhibit cancer growth. Ketones can inhibit cancer-cell growth even when glucose levels are high, prolonging by more than half the survival of mice with metastatic cancer.14 A ketogenic diet has been shown to improve survival in research animals with cancer of the colon, prostate, and brain.15
Ketone Versus Insulin Actions
Dr. Benjamin Bikman (associate professor, Brigham Young University, Provo, Utah) contrasts the effects of ketones and insulin.
Dr. Bikman is most interested in the effects of ketones and insulin on the energy-producing organelles in cells: the mitochondria. A diet high in carbohydrates increases insulin levels in the bloodstream to increase glucose absorption into cells. But mitochondrial function is disrupted by the high levels of insulin.16 Liver cells exposed to high levels of insulin have smaller mitochondria and reduced mitochondrial energy production.17
Impaired insulin action (insulin resistance, frequently seen in obesity and type II diabetes) results in an increased production of free radicals by mitochondria, which further increases insulin resistance (a vicious cycle).18 Obese persons have smaller mitochondria in their skeletal muscles, resulting in impaired muscle energy.19
Ketones, by contrast, protect mitochondria.20 Rats put on a ketogenic diet double the amount of the antioxidant chemical glutathione, which protects mitochondria from free-radical damage.21
The mitochondria in the hippocampal area of the brain are significantly increased in rats fed a calorie-restricted ketogenic diet.22 Feeding ketones to mice substantially increases the number of mitochondria and insulin sensitivity.23
Alzheimer’s Disease Treatment
Dr. Mary Newport (neonatologist, St. Petersburg, Florida) specializes in medical care for newborn infants. She became interested in Alzheimer’s disease when her husband developed it in his early 50s.
When Dr. Newport gave her husband nutritional products that are readily converted to ketones, first coconut oil, and later MCTs (medium chain triglycerides), her husband’s behavior and performance on cognitive tests increased substantially.24 She found that the MCT oil gave higher levels of ketones, but the coconut oil had a more lasting ketogenic effect.
Dr. Newport created a website (www.coconutketones.com) and wrote the book Alzheimer’s Disease: What if There was a Cure to document her experience and to promote the use of ketones for Alzheimer’s disease victims.
Neurons in areas of the brain associated with Alzheimer’s disease require insulin to absorb glucose, and those areas show increased markers of Alzheimer’s disease (beta-amyloid and tau) when the areas become insulin resistant.25 Neurons deprived of energy from glucose due to insulin resistance could be a cause of Alzheimer’s disease.
Alzheimer’s disease victims frequently develop a strong craving for sweets, which may be a symptom of their brains’ inadequate supply of glucose due to brain-cell insulin resistance.26 Ketones can provide glucose-deprived neurons with a source of energy, thereby allowing the neurons to function and survive. Administering ketones to brain slices, or in mouse models of disease, has been shown to reduce telltale signs of Alzheimer’s disease27 and Parkinson’s disease.28 Ketones also increase blood flow to the brain.29
In a study of human adults with mild cognitive impairment, randomized to low or high carbohydrate diet, the low carbohydrate group showed memory improvement that was associated with elevated blood ketones.30 In a similar study, MCTs improved memory in cognitively impaired humans.31
Clinical trials of a ketogenic diet for Alzheimer’s disease have been difficult to arrange, more so because most clinical trials are sponsored by drug companies. Nevertheless, there is much scientific evidence that the dietary ketones Dr. Newport administered to her husband would produce the improvements she observed.
Dr. Eric Westman (associate professor of medicine, Duke University, Durham, North Carolina) has co-founded Heal Clinics (www.healclinics.com) to treat diabetes, obesity, and metabolic syndrome through a ketogenic diet.
Dr. Westman conducted a clinical trial in which type II diabetics were randomized to either a ketogenic diet or a low-calorie diet. Those on the ketogenic diet had greater reduction in glycated hemoglobin (-1.5% versus -0.5%), and greater reduction or elimination of diabetic drugs (95.2% versus 62%).32
Comparisons of a low-carbohydrate diet with a low-fat diet have shown that a low-carbohydrate diet is much more effective in reducing insulin resistance and other markers of metabolic syndrome,33 and more strongly reduced inflammatory factors.34
Dr. Westman has co-authored a review paper arguing that diabetics can best control blood glucose with a low-carbohydrate diet, whether or not protein is also reduced.35 The paper also argued that although plasma-saturated fatty acids do not correlate with cardiovascular disease, dietary carbohydrates elevate plasma fats more than dietary fats do.35
Nervous System Injury Treatment
Dr. Wolfram Tetzlaff (professor, University of British Columbia, Vancouver, Canada) has studied the effect of a ketogenic diet on central nervous-system injuries in rats.
Young (35-day-old) rats given a ketogenic diet for seven days after traumatic brain injury showed significant improvement in cognitive function and movement ability, but 75-day-old rats did not.36 The reason for the difference is believed to be greater transport of ketones into the brain of young rats compared to old rats.37
The antioxidant effects of ketones are believed to be strong in the early stages of injury, whereas the ability of ketones to substitute for glucose as an energy source is believed to be their main benefit later.38 Dr. Tetzlaff has shown that rats fed a ketogenic diet for 14 weeks following spinal-cord injury show better function and reduced spinal-cord damage.39
The brain’s ability to use glucose is impaired after traumatic brain injury, and the longer the brain is deprived of energy, the greater the impairment of cognitive function.40 Direct application of ketones to rat neurons has been shown to reduce free-radical damage.20
Why a Ketogenic Diet can Prevent Epilepsy
Dr. Susan Masino (professor of applied science, Trinity College, Hartford, Connecticut) is one of many researchers trying to understand why a ketogenic diet can prevent epilepsy.
A clinical trial found that less than half of epileptics had a greater than 50% reduction of seizures on a ketogenic diet, and 7% had at least a 90% reduction of seizures.41 But it has not been possible to predict which epileptic patients will or will not experience seizure reduction on a ketogenic diet.42 If the biological mechanism of the ketogenic diet against epilepsy were understood, it might be possible to achieve the same effect with a drug.43
Low levels of glucose in the brain (hypoglycemia) not compensated by ketones as an energy source results in seizure.44 A ketogenic diet not only provides the brain with ketones for energy, but increases energy-producing mitochondria, and reduces free-radical production by mitochondria.45 Dr. Masino has shown that a ketogenic diet reduces seizures through an increase in the energy-producing molecule ATP, and an associated increase in the sedative chemical adenosine, derived from ATP46 and through increased adenosine receptor activity.47
Dr. Masino has noted that inflammation is frequently seen in epilepsy.48 She has also studied the beneficial effects of a ketogenic diet in animal models of autism.49 Epilepsy is common in children with autism.49
Ketones for Athletics
Dr. Jeff Volek, RD (professor, Ohio State University, Columbus, Ohio) has challenged the idea that athletes should depend upon or load-up on carbohydrates prior to or during a competition.50
The amount of energy that even a thin person has stored as fat is tens of times greater than the amount of energy they have stored as carbohydrate (glycogen).50 Athletes frequently complain of “hitting the wall” (sudden fatigue) when their glycogen supply has been depleted. Dr. Volek has argued that there will be vastly more energy available if an athlete is adapted to using fat and ketones, rather than carbohydrate for energy.
Use of carbohydrate for energy depends on the PDH (pyruvate dehydrogenase) enzyme complex, whereas use of fat for energy depends on the enzyme PDK (pyruvate dehydrogenase kinase), which inhibits PDH.51 Six days of a high-fat/low-carbohydrate diet increases PDK activity five-fold.51 Full adaptation to fat and ketone use for energy can require weeks.50 Dr. Volek has shown that keto-adapted elite athletes more than double their rate of fat oxidation without a greater depletion of glycogen.52
Critics of Dr. Volek’s views point to evidence that athletic performance is only optimized by carbohydrates due to better oxidation economy by carbohydrates.53,54 A small New Zealand study of keto-adapted athletes showed that, despite a reduction in performance, the athletes experienced faster recovery, reduced inflammation, and other health benefits which caused the athletes to continue the high-fat/low-carbohydrate diet.55
It is a common misconception that eating fat necessarily makes a person fat. Sugar and other carbohydrates cause fatness much more than dietary fat.
Insulin is the ultimate cause of fatness. Carbohydrates raise insulin, which causes glucose and fat to be stored as fat. Dietary fat does not raise blood insulin. Careful examination of scientific reports inducing obesity by a “high-fat diet” typically show a diet high in both fat and carbohydrate.
In some persons (especially the obese), intestinal microorganisms cause a high-fat diet to induce chronic inflammation by causing a “leaky gut.” But the class of polyphenols known as proanthocyanidins (found in grapes and other foods),56 orange juice components,57 and omega-3 fatty acids (found in fish oil)58 can prevent this inflammation.
Several days or weeks may be required for the body to adapt to using fat and ketones for energy rather than glucose. This period of adaptation can initially involve tiredness and headaches (the “keto flu”). The glucose-insulin roller-coaster of carbohydrate addiction has withdrawal symptoms. It takes time to increase the PDK enzymes and decrease PDH enzymes. Fasting can assist with adaptation.
Ketone is a more efficient fuel than glucose, producing more energy, fewer free radicals, and less inflammation.59 Ketone supplementation has been shown to extend the lifespan of nematode worms.60 Long-lived mice are more adapted to using fat for energy rather than carbohydrates.61
The classic ketogenic diet to treat epilepsy is typically 80%-90% fat, the rest being protein and carbohydrate.62 Many people find this diet unpalatable, although a web search for “ketogenic diet recipes” will reveal many strategies for making the diet appealing.
A ketogenic diet can also be made more palatable by using medium-chain triglycerides (MCTs, found in coconut oil) as a source of fat. MCTs can be as effective in controlling epilepsy as the long-chain triglycerides in common saturated fats.63 The ten-carbon chain-length MCT is the most effective.64
MCTs are rapidly metabolized, are not stored as fat, enter mitochondria without needing L-carnitine, and are more satiating than other forms of saturated fat.65 MCTs have been used to assist weight loss.65 Unlike long-chain fatty acids, MCTs do not become “ectopic fat” that can cause insulin resistance and inflammation.67 MCTs should not be used as cooking oil due to degradation at high temperature.66
The Atkins diet, which only restricts carbohydrates without any restriction in the amount of dietary protein or fat, is much more palatable, and can be as effective as the classic ketogenic diet for some epilepsy victims.67
Moreover, a 2007 study of four popular weight-loss diets showed that the Atkins diet was more effective than the other three diets.68 Contrary to what is commonly believed, dietary protein does not result in much glucose production.69
Direct consumption of ketones may be beneficial in some cases. A web search for “ketone supplements” will show there are many products being marketed to enhance athletic performance, promote weight loss, etc. Deep-sea diving Navy SEALS consume ketone supplements to prevent underwater seizures based on experiments on rats in high-pressure containers, showing that ketone supplements protected the rats from seizures.70
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- Neal EG, Zupec-Kania B, Pfeifer HH. Carnitine, nutritional supplementation and discontinuation of ketogenic diet therapies. Epilepsy Res. 2012;100(3):267-71.
- Kossoff EH, Al-Macki N, Cervenka MC, et al. What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy. Epilepsia. 2015;56(9):1337-42.
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- McNally MA, Pyzik PL, Rubenstein JE, et al. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics. 2009;124(2):e300-4.
- Nei M, Ngo L, Sirven JI, et al. Ketogenic diet in adolescents and adults with epilepsy. Seizure. 2014;23(6):439-42.
- Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-6.
- Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415-21.
- Seyfried TN, Shelton LM. Cancer as a metabolic disease. Nutr Metab (Lond). 2010;7:7.
- Frezza C, Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol. 2009;19(1):4-11.
- Kaipparettu BA, Ma Y, Park JH, et al. Crosstalk from non-cancerous mitochondria can inhibit tumor properties of metastatic cells by suppressing oncogenic pathways. PLoS One. 2013;8(5):e61747.
- Kiebish MA, Han X, Cheng H, et al. In vitro growth environment produces lipidomic and electron transport chain abnormalities in mitochondria from non-tumorigenic astrocytes and brain tumours. ASN Neuro. 2009;1(3).
- Huysentruyt LC, Seyfried TN. Perspectives on the mesenchymal origin of metastatic cancer. Cancer Metastasis Rev. 2010;29(4):695-707.
- Poff AM, Ari C, Arnold P, et al. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer. 2014;135(7):1711-20.
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- Srivastava S, Kashiwaya Y, King MT, et al. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB J. 2012;26(6):2351-62.
- Newport MT, VanItallie TB, Kashiwaya Y, et al. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s disease. Alzheimers Dement. 2015;11(1):99-103.
- Kleinridders A, Ferris HA, Cai W, et al. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014;63(7):2232-43.
- Henderson ST, Vogel JL, Barr LJ, et al. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009;6:31.
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