Free Shipping on orders over $99

Medium Chain Triglycerides for Neurodegenerative Diseases

Behaviour, Weight loss, Epilepsy, Mental Health | February 10, 2015 | Author: The Super Pharmacist

alzheimers, diet, mental health, parkinsons

Medium Chain Triglycerides for Neurodegenerative Diseases

Almost a hundred years ago, pioneering researchers found that many patients with epilepsy remained free of seizures while fasting and for several months after a return to a normal diet.1 The effect was attributed to a condition called "ketonaemia" (excessive ketones in the blood) induced by fasting. After a few days of fasting, or of drastically reduced carbohydrate consumption (below 20-50 g/day), glucose reserves become insufficient for the supply of glucose to the brain.2,3 The brain normally utilises glucose and cannot use fat as an energy source because free fatty acids cannot cross the blood-brain barrier. After 3–4 days without access to glucose, the brain is ‘forced’ to find some type of alternative energy source.2-5 This alternative energy source turns out to be something called ketone bodies (KB). In the absence of glucose, the liver is forced to breakdown dietary fat for energy. As a result of this breakdown process, ketone bodies, or simply, ketones, are formed and accumulate in the blood.

There are three ketone bodies: acetoacetate, β-hydroxybutyric acid and acetone.6 This kind of energy production is called ketogenesis. Interestingly, the KBs (ketones) are able to produce a higher quantity of energy than glucose due to the changes in mitochondrial metabolism that they induce.7-9 Dietary fats and oils are made from two molecules: glycerol (a type of alcohol) and fatty acids. When glycerol is joined to 3 fatty acids, it is called a "triglyceride". Triglycerides account for about 95% of all dietary fat.12 The chain lengths of the fatty acids in naturally occurring triglycerides vary from 2 to 22 carbon atoms in length. Long chain triglycerides contain long chain fatty acids ranging from 12 to 22 carbon atoms in length. Medium chain triglycerides contain fatty acids that are 6 to 10 carbon atoms long. Early scientists proposed that a "ketogenic diet" (KD) – very high in fat – which increases levels of circulating ketones, should be used in the treatment of epilepsy.10

The classic KD contains a 4:1 ratio of fat to combined protein and carbohydrate.11 The KD is designed to increase the body's dependence on fat rather than glucose for energy. It mimics the fasting state. Thus, a 4:1 KD diet means that the diet contains 4 grams of fat for every gram of protein plus carbohydrate. Since each gram of fat provides 9 calories and each gram of protein and carbohydrate provides 4 calories, 90% of the total calories in a 4:1 KD come from fat. Most of the fat in the classic KD is derived from long-chain triglycerides. A modification of this diet was introduced in the 1970s using medium-chain triglycerides (MCT) as an alternative fat source.13 MCT yield more ketones per kilocalorie of energy than then long-chain triglycerides, are absorbed more efficiently, and are carried directly to the liver from the digestive tract. This increased ketogenic potential means less total fat is needed in the MCT diet to preserve the increased level of circulating ketones. Less total fat allows more carbohydrate and protein to be included in the diet, thus making it more palatable.14

What Are the Benefits of an MCT Diet?

The efficacy of the KD in treating epilepsy has been well established for many decades, and the very low carbohydrate diet became even more widely known in the 1970s for its efficacy in weight-loss therapy – especially as the Atkins diet. Recent work over the last decade or so has provided evidence of the therapeutic potential of the different forms of the KD in numerous diseases, such as Type 2 diabetes, Alzheimer’s Disease, Parkinson’s, Amyotrophic Lateral Sclerosis, brain trauma, autism, and cancer.


The KD has been proven effective in patients with intractable epilepsy. The treatment is typically recommended when traditional antiepileptic drugs have failed or when these drugs cause unacceptable side effects.16 The clinical efficacy of the KD has been verified in numerous studies, both in the United States and internationally.17-23 The success rate of the KD in controlling refractory seizures is at least as good as, and often better than that of the “new” antiepileptic drugs.20 In general, at least half of all patients treated with the KD will exhibit a 50% or greater reduction of seizure frequency. Any seizure type may respond to the diet,24 but some generalised seizure types (e.g., myoclonic, atonic, generalized tonic–clonic, and even infantile spasms25) may be reduced preferentially.

The KD is effective in people of all ages, although it may be maximally effective in the toddler and school-age child.18,26,27 Interestingly, the success rate of the KD in recent years is similar to that observed during the early decades of its use.28 Perhaps most important, intriguing recent data indicate that a ketogenic diet sometimes can be discontinued without concomitant loss of seizure control.16,21 The efficacy of the MCT diet is excellent and is similar to that achieved by the KD, which has been verified in several subsequent retrospective, prospective, and randomized studies. These studies have shown that more than 50% of the children had achieved >50% reduction in seizure control.13, 29-35 Four studies directly comparing the KD with the MCT diet found no difference in seizure control.31-34 However, the literature frequently documents the associated gastrointestinal side effects from the MCT diet, such as diarrhea, vomiting, bloating, and cramps.13, 29-34 For this reason, the MCT diet has been an underutilised diet therapy for intractable epilepsy among children.

Weight Loss Therapy

There is strong supportive evidence that the use of the KD in weight-loss therapy is effective, but theories conflict as to how these diets work. Some researchers believe weight loss simply results from reduced caloric intake, probably due to the increased satiety effect of protein.36 Satiety is a position of being and feeling full to the point where no more food is required for the body to be satisfied. However, this does not explain study findings that individuals who follow a low-carbohydrate diet lose more weight during the first 3–6 months compared with those who follow balanced diets.37-39  A plausible explanation for improved weight loss may be the appetite-suppressant action of ketosis.40

Cardiovascular Disease

Considerable doubt still exists as to the cardiovascular benefits of a low carb, high fat diet. The majority of recent studies, however, seem to demonstrate that the reduction of carbohydrates to levels that induce physiological ketosis can actually lead to significant benefits in blood lipid profiles.41-43 The very low carbohydrate KD effect seems to be particularly marked on the level of blood triglycerides,44,45 but there are also significant positive effects on total cholesterol reduction and increases in high-density lipoprotein.44-46

Type 2 Diabetes

Insulin resistance is the primary feature underlying type 2 diabetes (T2D). A person with insulin resistance will divert a greater proportion of dietary carbohydrate to the liver where much of it is converted to fat, as opposed to being oxidised for energy in skeletal muscle.47 This greater conversion of dietary carbohydrate into fat, much of it entering the circulation as saturated fat, is a metabolic abnormality that significantly increases risk for diabetes and heart disease. Thus, insulin resistance functionally manifests as ‘carbohydrate intolerance.’ When dietary carbohydrate is restricted to a level below which it is not significantly converted to fat (a threshold that varies from person to person), signs and symptoms of insulin resistance improve or often disappear completely. In a study of 66 obese patients with T2D who were prescribed a well-formulated KD for 56 weeks, significant improvements in both weight loss and metabolic parameters were seen at 12 weeks and continued throughout the 56 weeks as evidenced by improvements in fasting circulating levels of glucose (−51%), total cholesterol (−29%), high-density lipoprotein–cholesterol (63%), low-density lipoprotein–cholesterol (−33%) and triglycerides (−41%).48


In one animal study,49 24 mice were injected subcutaneously with human gastric cancer cells. The animals were then randomly split into two feeding groups and fed either a KD or a standard diet (SD). The KD consisted of 35.5% fat, 13.0% protein, and 0.2% carbohydrates, 21.45% MCT, and was enriched with omega-3 fatty acids. Tumour growth in the KD group was significantly slowed and survival in the KD group was significantly prolonged compared to that in the SD group. In another study,50 mice were implanted with either human astrocytoma or human glioma cells. The mice were then randomly assigned to one of three diet groups: 1) an unrestricted standard diet (SD), 2) an unrestricted KD (KetoCal®), or 3) a restricted KD designed to reduce body weight by about 20%. The astrocytoma group of mice that received a KD showed a 65% reduction in tumour growth rate compared to the astrocytoma group that received an unrestricted SD. The glioma group showed a 35% reduction in tumour growth compared to the glioma group fed a SD. Mean survival was also significantly longer in the KD mice. In contrast to normal tissues, which can metabolise glucose, fatty acids and ketones, many tumours depend heavily on glucose for their metabolic demands and ferment it to lactate - even under sufficient oxygen supply.51,52 Tumour cells often lack the ability to use fatty acids or ketones as an energy source and could even be harmed by them.53-55 As of yet, there are no randomised controlled trials on the effects of a KD on patients with cancer. Evidence on the influence of a very low carbohydrate KD on patient survival is still anecdotal. In summary, perhaps through glucose ‘starvation’ of tumour cells and by reducing the effect of direct insulin-related actions on cell growth, ketogenic diets show promise as an aid in at least some kind of cancer therapy.

Alzheimer's Disease

Ever since the first description of pre-senile dementia by Alois Alzheimer in 1907,56 the presence of cognitive impairment together with the formation of senile plaques and neurofibrillary tangles have been regarded as the defining clinico-pathologic features of Alzheimer's disease (AD).57-59   Various theories have been proposed to explain the development of AD including:60

Senile plaques: AD is characterised by the accumulation of toxic protein fragments called amyloid beta. Amyloid beta is the main component of the senile plaques seen in the brains of Alzheimer's patients. These amyloid plaques are toxic to nerve cells.

Neurofibrillary tangles: Tau proteins act to stabilise microtubules in nerve axons. However when tau is, it is unable to bind and the microtubules become unstable and begin disintegrating. The unbound tau clumps together in formations called neurofibrillary tangles. Neurofibrillary tangles function much the same as amyloid beta aggregates in that they initiate several process that lead to cellular dysfunction and death.

Mitochondrial dysfunction: Mitochondria generate the energy required for cellular function. Mitochondrial dysfunction has been implicated in AD.

Inflammation: High levels of amyloid beta in the brain activate the body’s immune response, resulting in inflammation that damages neurons.

Oxidative stress: Oxidative stress is a process in which highly reactive molecules called free radicals damage cellular structures. Free radicals are byproducts of normal metabolism, but during states of metabolic abnormality such as mitochondrial dysfunction, they are created more rapidly and in greater quantity.

Other theories: Other hypotheses include an excess of excitatory glutaminergic neuro-transmission and chronic infection with the Spirochetes bacterium. Acetylcholine deficit is now viewed as a consequence of the generalised brain deterioration observed in AD, rather than a direct cause.

Cerebral glucose hypo-metabolism: Recent scientific literature has introduced yet another theory regarding the pathogenesis of AD. Emerging evidence suggests that cerebral glucose hypometabolism may underlie or contribute to the development of AD. The concept that impaired brain glucose metabolism may contribute to the development of AD has been developed by several independent research groups over at least the past 25 years.7,61-69 Nowadays, the most common approach to studying brain metabolism by positron emission tomography (PET) using the tracer - 18F-fluorodeoxyglucose (FDG). PET studies have long pointed to lower brain glucose metabolism in AD.

An overview of the now extensive literature on brain metabolism shows that global cerebral metabolic rate of glucose (CMRg) is ~20–25% lower in AD, with a more marked difference in some regions. In AD, the earliest difference in CMRg is probably in the hippocampus, which is intimately involved in memory processing.70 After the hippocampus, lower CMRg in AD is seen most commonly in the posterior cingulate, temporal and parietal lobes and, later on, in the frontal lobes.71 In the relatively few studies of brain glucose metabolism in mild cognitive impairment (MCI), global CMRg is lower than in controls but the difference is less than in moderate to severe AD. It is still unclear whether or not healthy aging is truly associated with declining CMRg, but this is an important issue to resolve. The question has always been, is this a cause or an effect? Until recently, the thinking has been that if the neurons are dying, they are going to need less fuel. In that view, glucose hypometabolism is purely a consequence of the disease. However, there are emerging lines of evidence suggesting that a metabolic problem is also present in the neurons before the clinical symptoms start to develop.70,73 It is important to note that there are links between T2D and AD.74 People with T2D are at higher risk of developing AD, and several hypotheses have been proposed to explain this observation. For example, high insulin levels, such as those observed in people with insulin resistance, might prevent the brain from degrading Aβ protein. Insulin is a critical hormone that decides which fuel is going to be used in the brain.70 In T2D glucose levels are elevated, so fuel availability is not the problem. The problem is that the cells that should be using the glucose are unable to do so. This is what we call insulin resistance. We always thought that the brain was not affected by insulin or by insulin resistance. However, in the past decade or so, it has become clearer that, in fact, one of the reasons why people with T2D appear to be more vulnerable to AD is because insulin appears to play a role in the brain. There is mounting evidence that insulin-signaling pathways are downregulated in the brains of people with AD.75 That is basically what we refer to as insulin resistance and has led some people to propose that perhaps AD might be thought of as "type 3 diabetes."75 A ketogenic diet will raise the level of ketones and switch brain fuel utilisation toward things like β-hydroxybutyrate and acetoacetate, which are the 2 major ketone bodies. Will patients with AD or its frequent precursor state, mild cognitive impairment, be able to adhere to such a diet? Will they be able to maintain stable ketosis, or will they abandon the diet because it is just too demanding?72 A prescription medical food that consists of medium-chain triglycerides has been developed in the US by manufacturer, Accera, and is called Axona. Like drugs, "medical foods" are regulated by the US FDA, but agency's approval standards for this category are far less rigorous than for drugs. According to the Alzheimer's Association, there are just five FDA-approved drugs to treat the symptoms of Alzheimer's, compared with the dozens available for conditions like cancer or heart disease. And scientists say none of the Alzheimer's drugs provide patients any lasting protection from the gradual advance of the disease's symptoms. This non-drug prescribed therapy is designed for the specific metabolic needs of patients with mild to moderate AD. Axona works by supplying the fatty acids that the liver turns into ketones that the mild to moderate Alzheimer’s brain needs to power its activities. Diminished glucose metabolism has been demonstrated in AD. Ketones are the brain’s back-up fuel.

Parkinson’s Disease

The pathogenesis of sporadic Parkinson’s disease (PD) remains unresolved, but numerous studies suggest that the primary cause is excitotoxic degeneration of dopaminergic neurons in the brain region called the substantia nigra, leading to abnormalities of movement and cognition. It has been suggested that an impairment of mitochondrial function involving the substantia nigra plays an important contributory role in the initiation and progression of PD.76 A neurotoxic substance called MPP+, both in vitro and in vivo, produces death of dopaminergic substantia nigral cells, producing a syndrome indistinguishable from PD.77 One in vitro study demonstrated that addition of D-β-hydroxybutyrate (one of the ketone bodies) protected cultured brain neurons from MPP+ toxicity.77  In another study, infusion of β-hydroxybutyric acid in mice conferred partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP (a neurotoxin precursor to MPP+).78 Moreover a KD protected dopaminergic neurons of the substantia nigra from yet another neurotoxic agent in a rat model of PD.79 A 2005 study demonstrated that in humans, able to prepare a “hyperketogenic” diet at home and adhere to it for 28 days, the high level of ketones was related to improvements in the Unified Parkinson’s Disease Rating Scale scores.80

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects spinal and cortical motor neurons, leading to progressive weakness and loss of skeletal muscle. Affected subjects die within 2 to 5 years of symptom onset. Death usually occurs from respiratory paralysis. At the moment, there are no effective treatments for ALS, and the only US FDA approved pharmacological therapy is limited to riluzole that causes only a modest decrease of the disease progression and increases survival by only 2 to 3 months.81 As in other neurodegenerative disorders, the probable mitochondrial involvement makes the KD a promising synergic tool for the treatment of ALS.82 Recently, researchers have demonstrated that in an ALS mouse model, the administration of a KD led to a higher motor neuron survival and a significant delay in progression of motor impairment.83 Another study reported that supplementation with a precursor of KB (caprylic acid) improved mitochondrial function and motor neuron count in an ASL mouse model.84


Estimates indicate that autism spectrum disorder (ASD) affects at least 1 in 160 individuals.85 Diagnosis involves three core symptoms: impaired social interactions, stereotyped repetitive behaviours and communication deficits.86 Given the ubiquitous presence of metabolic abnormalities in neurological disorders,87 including autism,88 metabolism-based therapies such as the KD are of great interest. This rationale is supported by a thus far singular prospective clinical report of a pilot study conducted on 30 children, four to ten years old.89 The diet was applied intermittently (four weeks on and two weeks off) for six months, and parents evaluated behavior using the Childhood Autism Rating Scale. Of those children who maintained the diet (18/30), 11% had significant improvement, 44% average improvement, and 44% mild improvement. In another study, the behavioral effects of a KD was tested on BTBR mice.90 The BTBR T+ tf/j (BTBR) strain of mice, developed through the early and mid-20th century, was recently characterised as having an autism-like behavioral phenotype.91 These mice have low sociability in a number of tests, reduced communication, and elevated self-directed behavior compared to typical strains. The study demonstrated that ketogenic diet-fed BTBR mice showed increased sociability in a three-chamber test, decreased self-directed repetitive behavior, and improved social communication of a food preference.

Traumatic Brain Injury (TBI)

Hypoxic/ischemic brain injury leads to a decrease in oxidative metabolism by reducing oxygen availability.92,93 Ketone administration ameliorates many of the sequelae of this process, including lactate generation, and free radical damage.94,95 One study demonstrated that β-hydroxybutyrate prolonged the survival time in rat models of hypoxia, anoxia and global ischemia.96 They further showed that β-hydroxybutyrate reduced infarct size after middle cerebral artery occlusion, irrespective of whether β-hydroxybutyrate administration was delayed. More recently, TBI models have been developed.97,98 TBI is associated with impaired cerebral energy production with prolonged glucose metabolic depression and reduction of ATP production. Cerebral injury is further exacerbated by free radical production.99 As such, under these conditions of impaired glycolytic metabolism, shifting the brain toward ketone metabolism may limit the extent of cerebral injury.96, 100-102 One study demonstrated that administration of intravenous β-hydroxybutyrate after TBI in adult rats led to an increase in uptake of β-hydroxybutyrate and alleviated the decrease in ATP after injury.97 That study also demonstrated age-dependence of the neuroprotective effect of ketones on brain injury. Ketogenic neuroprotection was shown among postnatal day 35 (PND35) and PND45 rats after TBI, but not in PND17 and PND65 animals. Another study corroborated this age-dependent effect where administration of a KD for 7 days beginning immediately after TBI significantly improved both motor and cognitive recovery in PND35 rats but not in PND75 animals.98

What Does a Typical MCT Diet Contain?

Palm kernels and palm kernel oil Medium chain fatty acids contain between 6 and 12 carbon chains.103 They are:

  • C6 – Caproic Acid
  • C8 – Caprylic Acid
  • C10 – Capric Acid
  • C12 – Lauric Acid

Medium chain triglycerides (MCT) are made up of these fatty acids. Coconut oil and palm kernel oil are the top sources of MCTs. Both have about 11 grams of saturated fat in 1 tablespoon of oil. Out of the total saturated fat, you'll get 7.4 grams of MCTs from a tablespoon of palm kernel oil and 7.9 grams from coconut oil. Although MCTs are found in coconut oil, they are even more predominant in other places in nature, such as goat’s milk. This is reflected in their names, taken from “capra,” which means “goat.”

Coconut oil contains all four MCTs. In addition, it contains a small percentage of longer chain fatty acids. The most predominant MCT found in coconut oil, however, is lauric acid. Coconut oil is about 50% lauric acid, making it nature’s richest source of lauric acid.104 Cow, sheep and goat milk all contain MCTs. Of these, by far the highest MCT content is present in sheep’s milk (about 25%). It contains twice as much lauric acid as goat’s milk and nearly three times as much as cow’s milk. Although sheep’s milk may not be readily available, but grocers do carry sheep’s milk yoghurt.105 Individuals who are lactose-intolerant will be able to tolerate goat’s milk about half the time because it contains less lactose than cow’s milk. Some of the world’s most famous cheeses are made from sheep’s milk: Rocquefort (France), Pecorino (Italy), Kefalograviera and Fetta (Greece) and Manchengo (Spain) to name just a few. Here again the cheese making process makes the food less likely to cause digestive problems, as the milk proteins that cause allergies have been removed.105

MCT oil, on the other hand, is not an oil found in nature, but is manufactured by machine to separate out the medium chain fatty acids from the rest of the oil. The fatty acids are extracted through an industrial process of “fractionation.” MCT oils generally contain only the capra fatty acids. Lauric acid is either missing, or present in minuscule amounts.104 MCT KD (medium chain triglycerides/ketogenic diet) is not diet ratio related. This diet depends on the percentage of calories from MCT oil which are the major ketone resource, for example, a representative MCT KD may be: 1800 kcal 60% MCT ketogenic diet."106 The percentage of MCT, long chain fat, carbohydrate, and protein can be adjusted for better tolerance. When using the MCT KD, all foods are allowed except foods rich in carbohydrate. Sugar and all sugar-containing foods must be avoided. Food exchanges are used to calculate the MCT diet. Food is divided into six food groups as follows: starch/grain, dairy (skim milk/nonfat yogurt), meat/egg/poultry/seafood, vegetables/fruits, fat, and MCT oil. MCT KD is divided into three meals plus three snacks per day. One gram of MCT oil is equal to 8.3 kcal. MCT oil can be mixed with milk or made into a salad dressing as it has no taste or smell. MCT oil cannot be used for frying at high temperature and should be stored in a dark glass container to maintain its biochemical properties.106 Sample menus for a 1500 kcal 60% MCT, 11% LCT, 19% CHO, and 10% protein KD (daily nutrient intake: 108.5 g MCT, 18.4 g LCT, 71.2 g CHO, and 37.5 g protein) are presented in Table 1 and 

Are There Any Adverse Effects of the MCT Diet?

In some studies, the MCT diet has been associated with side effects such as diarrhea, vomiting, bloating, and cramps. These side effects can be minimized or eliminated by starting with very small doses (i.e., about 1/4 teaspoon several times daily), and increasing the dose as tolerated. Before long, MCT can be taken by the tablespoonful. MCT oil can be used as a salad dressing, and as a cooking oil.107 MCTs are quite safe when consumed at a level of up to 50% of total dietary fat.108 Late-onset complications can include osteopenia, kidney stones, cardiomyopathy, and iron-deficiency anemia.109 Complications are usually transient and successfully managed by careful follow-up and conservative strategies.  Australia’s best online discount chemist


1. Geyclin HR. Fasting as a method of treating epilepsy. Medical Record 1921;99:1037-9.

2. Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GFJr. Brain metabolism during fasting.J Clin Invest1967; 46: 1589–1595.

3. Felig P, Owen OE, Wahren J, Cahill GF., Jr. Amino acid metabolism during prolonged starvation. Journal of Clinical Investigation. 1969;48(3):584–594.

4. Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF., Jr. Liver and kidney metabolism during prolonged starvation. The Journal of Clinical Investigation. 1969;48(3):574–583.

5. George FC. Fuel metabolism in starvation. Annual Review of Nutrition. 2006;26:1–22.

6. Fukao T, Mitchell G, Sass JO, et al. Ketone body metabolism and its defects. Journal of Inherited Metabolic Disease. July 2014;37(4):541-51.

7. Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukotrienes and Essential Fatty Acids. 2004;70(3):309–319.

8. Sato K, Kashiwaya Y, Keon CA, et al. Insulin, ketone bodies, and mitochondrial energy transduction. The FASEB Journal. 1995;9(8):651–658.

9. Kashiwaya Y, Sato K, Tsuchiya N, et al. Control of glucose utilization in working perfused rat heart. The Journal of Biological Chemistry. 1994;269(41):25502–25514.

10. Wilder RM. The effect of ketonaemia on the cause of epilepsy. Mayo Clinic Bulletin 1921;2:307-14.

11. Barclay L, Gandey A. New Finding Adds Weight to Ketogenic Diet for Childhood Seizures. Medscape. Published 3 June 2010. Accessed 4 Feb 2015.

12. Triglycerides.$File/Triglycerides.pdf Updated 21 Mar 2014. Accessed 6 Feb 2015.

13. Huttenlocher PR, Wilborne AJ, Signore JM. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 1971;21:1097-103.

14. Neal EG, Chaffe H, Schwartz RH, Lawson, MS, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia. 2009;50: 1109–1117.

15. File:220 Triglycerides-01.jpg. By OpenStax College [CC BY 3.0 (], via Wikimedia Commons. Updated 13 Dec 2013. Accessed 6 Feb 2015.

16. Freeman JM, Freeman JB, Kelly MT. The ketogenic diet: a treatment for epilepsy. 3rd ed. New York, NY: Demos Health; 2000.

17. Freeman J, Vining E, Pillas D, Pryzik P, Casey J, Kelly M. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998;102:1358–1363.

18. Vining EG, Freeman JM, Ballaban-Gil K, et al. A Multicenter Study of the Efficacy of the Ketogenic Diet. Arch Neurol. 1998;55(11):1433-1437.

19. Katyal NG, Koehler AN, McGhee B, Foley CM, Crumrine PK. The ketogenic diet in refractory epilepsy: the experience of Children's Hospital of Pittsburgh. Clin Pediatr. 2000;39:153–159.

20. LeFevre F, Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: a systematic review of efficacy. Pediatrics. 2000;105

21. Hemingway C, Freeman JM, Pillas DJ, Pyzik PL. The ketogenic diet: a 3- to 6-year follow-up of 150 children enrolled prospectively. Pediatrics. 2001;108:898–905.

22. Coppola G, Veggiotti P, Cusmai R, et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res. 2002;48:221–227.

23. Levy R, Cooper P. Ketogenic diet for epilepsy. Cochrane Library. 2003:3.

24. Maydell BV, Wyllie E, Akhtar N, et al. Kotagal. Efficacy of the ketogenic diet in focal versus generalized seizures. Pediatr Neurol. 2001;25:208–212.

25. Kossoff EH, Pyzik PL, McGrogan JR, Vining EPG, Freeman JM. Efficacy of the ketogenic diet for infantile spasms. Pediatrics. 2002;109:780–783.

26. Sirven J, Whedon B, Caplan D, Liporace J, Glosser D, O'Dwyer J, Sperling M. The ketogenic diet for intractable epilepsy in adults: preliminary results. Epilepsia. 1999;40:1721–1726.

27. Nordli DR, Jr, Kuroda MM, Carroll J, Koenigsberger DY, Hirsch LJ, Bruner HJ, Seidel WT, DeVivo DC. Experience with the ketogenic diet in infants. Pediatrics. 2001;108:129–133.

28. Kinsman SL, Vining EPG, Quaskey SA, Mellits D, Freeman JM. Efficacy of the ketogenic diet for intractable seizure disorders: review of 58 cases. Epilepsia. 1992;33:1132–1136.

29. Trauner DA. Medium-chain triglyceride (MCT) diet in intractable seizure disorders. Neurology 1985;35:237-8.

30. Sills MA, Forsythe WI, Haidukewych D, MacDonald A, Robinson M. The medium-chain triglyceride diet and intractable epilepsy. Arch Dis Child 1986;61(Suppl. 8):1168-72.

31. Schwartz RH, Eaton J, Bower BD, Aynsley-Green A. Ketogenic diets in the treatment of epilepsy: Short-term clinical effects. Dev Med Child Neurol 1989;31:145-51.

32. Sell E, Liu YMC, Donner E, Curtis R. The medium-chain triglyceride ketogenic diet for the treatment of refractory lesional epilepsy in children. Epilepsia 2005;46:234.

33. Liu YM. Medium-chain triglyceride (MCT) ketogenic therapy. Epilepsia 2008;49 Suppl. 8:33-6.

34. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 2009;50:1109-17.

35. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. The ketogenic diet for the treatment of childhood epilepsy: A randomized controlled trial. Lancet Neurol 2008;7:500-6.

36. Westerterp-Plantenga MS, Nieuwenhuizen A, Tome D, Soenen S, Westerterp KR. Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr 2009; 29: 21–41.

37. Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003; 88: 1617–1623.

38. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR et al. Comparison of the atkins, zone, ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: The A TO Z weight loss study: a randomized trial. JAMA 2007; 297: 969–977.

39. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I et al. Weight loss with a low-carbohydrate, mediterranean, or low-fat diet. N Engl J Med 2008; 359: 229–241.

40. Johnstone AM, Horgan GW, Murison SD, Bremner DM, Lobley GE. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr 2008; 87: 44–55.

41. Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003; 88: 1617–1623.

42. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I et al. Weight loss with a low-carbohydrate, mediterranean, or low-fat diet. N Engl J Med 2008; 359: 229–241.

43. Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009; 44: 297–309.

44. Paoli A, Cenci L, Fancelli M, Parmagnani A, Fratter A, Cucchi A et al. Ketogenic diet and phytoextracts comparison of the efficacy of mediterranean, zone and tisanoreica diet on some health risk factors. Agro Food Ind Hi-Tech 2010; 21: 24.

45. Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gomez AL, Scheett TP et al. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr 2002; 132: 1879–1885.

46. Volek JS, Sharman MJ, Forsythe CE. Modification of lipoproteins by very low-carbohydrate diets. J Nutr 2005; 135: 1339–1342.

47. Jornayvaz FR, Samuel VT, Shulman GI. The role of muscle insulin resistance in the pathogenesis of atherogenic dyslipidemia and nonalcoholic fatty liver disease associated with the metabolic syndrome. Annu Rev Nutr 2010; 30: 273–290.

49. Dashti HM, Al-Zaid NS, Mathew TC, Al-Mousawi M, Talib H, Asfar SK, et al. Long term effects of ketogenic diet in obese subjects with high cholesterol level. Mol Cell Biochem 2006; 286: 1–9.

50. Otto C, Kaemmerer U, Illert B, Muehling B, Pfetzer N, Wittig R, et al. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides. BMC Cancer 2008; 8: 122.

51. Seyfried BT, Kiebish M, Marsh J, Mukherjee P. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet. J Cancer Res Ther 2009; 5 (Suppl 1), S7–S15.

52. Warburg O, Minami S. Versuche am überlebenden Carzinom-Gewebe. Klin Wochenschr 1923, 2:776–777.

53. Warburg O: On the origin of cancer cells. Science 1956, 123:309–314.

54. Buzzai M, Bauer DE, Jones RG, Deberardinis RJ, Hatzivassiliou G, Elstrom RL, Thompson CB: The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene 2005, 24:4165–4173.

55. Fine EJ, Miller A, Quadros EV, Sequeira JM, Feinman RD: Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2. Cancer Cell Int 2009, 29:14.

56. Skinner R, Trujillo A, Ma X, Beierle EA: Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg 2009, 44:212–6.

57. Alzheimer A. On a peculiar disease of the cerebral cortex. Allgemeine Zeitschrift fur Psychiatrie und Psychish-Gerichtlich Medicin 1907; 64: 146-148.

58. Armstrong RA. Plaques and tangles and the pathogenesis of Alzheimer’s disease. Folia Neuropathol 2006; 44: 1-11.

59. Khatchaturian ZS. Diagnosis of Alzheimer’s disease. Arch Neurol 1985; 42: 1097-1005.

60. Mirra SS, Heyman A, McKeel, D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991; 41: 479-486.

61. Alzheimer's disease. Life Extension. Published 2015. Accessed 7 Feb 2015.

62. Sims NR, Bowen DM, Neary D, Davison AN. Metabolic processes in Alzheimer’s disease: adenine nucleotide content and production of 14CO2 from [U-14C]glucose in vitro in human neocortex. J Neurochem.1983;41(5):1329–34.

63. Hoyer S, Oesterreich K, Wagner O. Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J Neurol.1988;235(3):143–8.

64. Heininger K. The cerebral glucose-fatty acid cycle: evolutionary roots, regulation, and (patho)physiological importance. Int Rev Neurobiol. 2002;51:103–58.

65. Blass JP. A new approach to treating Alzheimer’s disease.Ann N Y Acad Sci 2008;1147:122–8.

66. Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol.2004;490(1–3):97–113.

67. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease--is this type 3 diabetes?J Alzheimers Dis.2005;7(1):63–80.

68. Freemantle E, Vandal M, Tremblay-Mercier J, Tremblay S, Blachere JC, Begin ME, et al. Omega-3 fatty acids, energy substrates, and brain function during aging.Prostaglandins Leukot Essent Fatty Acids.2006;75(3):213–20.

69. Duara R, Barker WW, Chang J, Yoshii F, Loewenstein DA, Pascal S. Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.J Cereb Blood Flow Metab. 1992;12(6):927–34.

70. Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. 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.

71. Cunnane SC, Nugent S, Roy M, et al. Brain fuel metabolism, aging and Alzheimer's Disease. Nutrition. Jan 2011; 27(1): 3-20.

72. Mosconi L, Brys M, Switalski R, Mistur R, Glodzik L, Pirraglia E, et al. Maternal family history of Alzheimer’s disease predisposes to reduced brain glucose metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(48):19067–72.

73. Isaacson RS, Cunnane SC. Brain glucose hypometabolism, ketosis, and Alzheimer Disease: From controversy to consensus. Medscape. Published 27 Aug 2013. Accessed 7n Feb 2015.

74. Mamelak M. Sporadic Alzheimer's disease: the starving brain. J Alzheimer's Dis. 2012;31:459-474.

75. Swerdlow RH, Burns JM, Khan SM. The Alzheimer's disease mitochondrial cascade hypothesis. J Alzheimers Dis. 2010;20:S265-279.

76. Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease: is this type 3 diabetes? J Alzheimers Dis. 2005;7:63-80.

77. Camilleri A, Vassallo N. The centrality of mitochondria in the pathogenesis and treatment of Parkinson's disease. CNS Neuroscience & Therapeutics.2014;20(7):591–602.

78. Kashiwaya Y, Takeshima T, Mori N. D-β-Hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci USA. 2000 July 18;97:5440-5444.

79. Tieu K, Perier C, Casperson C, et al. D-3-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson’s disease. J Clin Invest 2003;112:892–901.

80. Cheng, X. Yang, L. An, B. Gao, X. Liu, and S. Liu. Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease. Brain Research. 2009; 1286: 25–31.

81. Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB. Treatment of parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology2005; 64: 728–730.

82. Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database of Systematic Reviews. 2002;(2)CD001447.

83. Siva N. Can ketogenic diet slow progression of ALS? The Lancet Neurology. 2006;5(6, article 476).

84. Zhao Z, Lange DJ, Voustianiouk A, et al. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neuroscience. 2006;7, article 29.

85. Zhao W, Varghese M, Vempati P, et al. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease. PLoS ONE. 2012;7(11)e49191.

86. Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 2012; 5: 160–179.

87. American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders IV, Text Revision. Washington DC: American Psychiatric Association.

88. Burnstock G, Krügel U, Abbracchio MP, Illes P. Purinergic signalling: from normal behaviour to pathological brain function. Prog Neurobiol 2011; 95: 229–274.

89. Frye RE, Rossignol DA. Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res 2011;69: 41R–47R.

90. Evangeliou A, Vlachonikolis I, Mihailidou H, et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003 Feb;18(2):113-8.

100. Ruskin DN, Svedova J, Cote JL, et al. Ketogenic Diet improves core symptoms of autism in BTBR mice. PLoS ONE 5 June 2013;8(6): e65021.

101. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, et al. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav 2008;7: 152–163.

102. Masuda R, Monahan JW, Kashiwaya Y. D-β-Hydroxybutyrate is neuroprotective against hypoxia in serum-free hippocampal primary cultures. J Neurosci Res. 2005;80:501–509.

103. Puchowicz MA, Emancipator DS, Xu K, et al. Adaptation to chronic hypoxia during diet-induced ketosis. Adv Exp Med Biol. 2005;566:51–57.

104. Hu ZG, Wang HD, Jin W, Yin HX. Ketogenic diet reduces cytochrome c release and cellular apoptosis following traumatic brain injury in juvenile rats. Ann Clin Lab Sci. 2009;39:76–83.

105. Hu ZG, Wang HD, Qiao L, Yan W, Tan QF, Yin HX. The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. Brain Injury. 2009;23:459–465.

106. Suzuki M, Suzuki M, Kitamura Y, Mori S, et al. Beta-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia. Jpn J Pharmacol. 2002;89:36–43.

107. Prins ML, Fujima LS, Hovda DA. Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. J Neurosci Res. 2005;82:413–420.

108. Appelberg KS, Hovda DA, Prins ML. The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat. J Neurotrauma 2009; 26: 497–506.

109. Hall ED, Andrus PK, Yonkers PA. Brain hydroxyl radical generation in acute experimental head injury. J Neurochem. 1993;60:588–594.

110. Biros MH, Nordness R. Eff ects of chemical pretreatment on posttraumatic cortical edema in the rat. Am J Emerg Med. 1996;14:27–32.

111. Go KG, Prenen GH, Korf J. Protective effect of fasting upon cerebralhypoxic-ischemic injury. Metab Brain Dis. 1988;3:257–263.

112. . Marie C, Bralet AM, Gueldry S, Bralet J. Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis. Metab Brain Dis. 1990;5:65–75.

113.. Enig MG. Know Your Fats : The Complete Primer for Understanding the Nutrition of Fats, Oils and Cholesterol. Silver Spring, MD: Bethesda Press; 2000.

114. Shilhavey B. MCT Oil vs. Coconut Oil: The Truth Exposed. Health Impact News. Published 4 June 2014. Accessed 8 Feb 2015.

115. How to get more MCTs (those Amazing Fats that Make you Thin) and other Fat Facts! Published 28 May 2013. Accessed 8 Feb 2015.

116. Liu YmC, Wang HS. Medium-chain triglyceride ketogenic diet: An effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomed J 2013;36:9-15.

117. Ward D. Medium chain triglycerides: Beneficial effects on energy, atherosclerosis and aging. Nutrition Review. Published 22 April 2013. Accessed 8 Feb 2015.

118. Traul KA, Driedger A, Ingle DL, et al. Review of the toxicologic properties of medium-chain triglycerides. Food Chem Toxicol. 2000;38:79-98.

119. Duchowny MS. Food for Thought: The Ketogenic Diet and Adverse Effects in Children. Epilepsy Curr. 2005 Jul; 5(4): 152–154.

backBack to Blog Home