MCT Research

Clinical trial summaries for KetoMCT™

MCT historical aspects: MCTs contain true medium chain fatty acids (MCFA; esterified to the glycerol backbone), having 8 and 10 carbons. MCTs were first studied as minor components of coconut oil beginning in 1906-1910. Their accumulation in adipose tissue was studied between 1906-1932 ^[1]. In 1951, they were utilized for intestinal malabsorption ^[2]. In 1958, they were first studied for growth, appetite, and weight management ^[3]. In the 1980s, they were extensively studied and marketed for sports applications. These MCFA are efficiently and rapidly digested (in the hepatic portal system). 

Sources of MCTs: Despite popular belief, coconut oil is not a good ketogenic fat as it contains 10-15% true C8 and C10 MCTs, and 45-78 percent of lauric acid, which is metabolized like longer chain fatty acids. MCTs are naturally abundant in mammalian milks such as those from man, cows, goats, sheep, horse, mouse, and rat ^[4-6]. MCTs are particularly abundant in goat milks and C6 (caproic), caprylic (C8), and C10 (capric) are named after goat (caprines).

MCT digestion, mobilization, metabolism, and conversion to ketone bodies: Unlike longer chain common fatty acids, MCFA are not stored in adult adipose tissue, but rather, preferentially converted in the liver, to the ketone bodies (KBs) beta-hydroxybutyrate (BHB; technically not a KB because it does not have a keto molecular group) and acetoacetate (AcAc). The process of creating KBs is known as ketogenesis. MCTs are stored in infant adipose tissue, to provide energy to infants in-between milk feeding. Mammalian milks are rich sources of MCTs, so having fat stores with MCTS is an evolutionary advantage ^[7]. These KBs are burned for energy very efficiently (following extra-hepatic mitochondrial degradation) in a process known as ketolysis, in the heart, kidney, central nervous system (brain) and skeletal muscle. MCTS are absolutely safe. The levels of KBs generated from MCTs are 3-4 orders of magnitude less than that occurring with diabetic ketoacidosis (DKA), a condition occurring in uncontrolled Type 1 diabetics leading to a lowering of blood pH and other serious sequelae.

KBs are particularly valuable energy sources when the body has limited carbohydrate stores (as in sustained exercise or after a fast), with KBs able to provide: 2% of the body's energy requirements after an over-night fast; and 30% after a 3-day fast (50% of basal energy requirements and 70% of brain energy ^[8]. MCFA increase plasma KBs for at least 8 hours after MCT intake ^[9]. MCFA will also spare protein degradation during sports and aging (reducing sarcopenia), and may improve insulin sensitivity, amongst many other physiological benefits.

Influence of chain length in MCTS and benefits of C8 MCTs: Early studies (using primitive instrumentation) in rats revealed that tricaproin (C6 MCT) and tricaprylin (C8 MCT) feeding does not lead to C6 nor C8 accumulation in adipose tissue (no C6 detected, and 1.5% C8 detected) ^{[1, 10]}. Tricaprin (C10 MCT) feeding led to a 15% accumulation in adipose ^[11], and trilaurin (C12) accumulated at 25% ^[1]. Later studies in rats confirmed that C10 minimally accumulates in rat adipose, in contrast to C12 and C14 ^[12]. Thus, as chain length increased, more MCT accumulated in adipose tissue. In baby rhesus monkeys, C8, C9, and C10 MCTs were compared ^[13]. Blood levels of KBs were considerably highest with C8 relative to C9 and C10 after 1-3 hours. Very recent clinical work presented at the 25th Canadian Conference on Fats and Oils in 2015, shows that tricaprylin (C8) was more ketogenic than MCTs containing mixtures of C8 and C10, and much more ketogenic than coconut oil in healthy adults ^{[14, 15]}. C8 MCTs have been particularly beneficial for improving cognition (see latter section).

Ketogenic diets and MCTs: The ketogenic diet (actually fasting) dates to biblical times: Jesus refers to fasting when a man suffers from what appear to be epileptic seizures (New Testament Matthew 17: 14-21; Mark 9: 14-29). Another important advantage to MCT consumption, is that KBs can be generated without the need to consume hard-to-follow, classical ketogenic diets containing very high amounts of fats (70-90% by weight), which may have adverse effects on blood lipids and digestion. These classical ketogenic diets were first developed to treat epilepsy in the 1920s ^[16], but have since been modified and developed for clinical applications, sports, and weight management (Atkins, Modified Atkins, Bernstein, Paleo, etc.). When consuming such high fat diets our bodies gradually become “keto-adapted” (as evidenced by a urine test) to effectively generate KBs (from amino acid and lipid catabolism) and burn ketones. For MCTs to be most effective, it is still desirable to consume a diet rich in healthy fats and low in carbohydrates (which is healthy, despite our USDA Food Pyramid guidelines), but this can be a challenge for some individuals to adhere to.

Weight Management:  MCTs have multiple actions regarding weight management. They increase energy expenditure, increase satiety (less food eaten at the next meal), decrease food intake, and increase fat intake. This results in a loss of body weight, by reducing fat mass, but not lean body mass (muscle). These effects have been documented in many studies and reviewed ^{[17, 18]}. Individuals consuming Atkins, Paleo, and Medifast types of dietary regimens, will appreciate that MCTs may be more effective, and easier to follow.

Cognition: There is intense interest in the ability of MCTs and particularly C8 MCTs to improve cognition in Alzheimer’s disease (AD), mild cognitive impairment, Parkinson’s disease ^[19], Huntington’s disease ^[20], Amyotrophic lateral sclerosis ^[21], epilepsy, multiple sclerosis ^[22], diabetes, stroke ^[23], and in healthy aging. Some work has been completed in pre-clinical animal models, some in human clinical trials, with many studies planned and in the Clinicaltrials.gov database. A few specific examples follow. The brain uses the most glucose of any organ in humans. In persons with AD there is about 25% less uptake of glucose ^[24]; and in healthy elderly, there is about 15% less uptake of glucose ^[25], in what is termed glucose cerebral hypometabolism ^[26] or Type III diabetes. The addition of C8 MCTs provides KB as an alternative energy source for the brain, resulting in improvements in a paragraph recall test in AD patients ^{[27, 28]}. In AD patients consuming C8 MCTs for 6 months or more, there were variable responses, but a slower rate of decline in Mini-Mental State Examination (MMSE) scores versus AD patients receiving pharmacotherapy alone ^[29]. MMSE scores were stable or improved over an 18.8 month follow-up period ^[30]. C8 MCTs are so potent and potentially beneficial; they are being developed as a drug to treat Alzheimer disease, as AC-1204 (follow-up to AC-1202 formulation) by Accera, Inc. Also suggestive of the benefits of MCTs, are studies with exogenous KBs. In animal models, exogenous KBs delayed Alzheimer-associated pathologies ^[31]. In a single human Alzheimer subject, exogenous KBs improved mood and cognitive and daily activity performance ^[32].

Sports: To date, ketogenic high fat-low carbohydrate diets have been found to be most beneficial for endurance athletes such as long distance runners ^{[33, 34]}. There are fewer studies evaluating the benefits of MCTs. But there are reasons to be optimistic. With MCTs, the advantages of weight management, energy for sustained sports activity, and cognitive benefits would be achieved rapidly, but without the need to be on a strictly ketogenic diet and without the typical two weeks required to keto-adapt to effectively using KBs as a primary energy source. It is possible one could yo-yo from high carbohydrate/low fat to low carbohydrate/high fat and still achieve the benefits of consuming MCTs. Also, with a classical ketogenic diet, one must not consume excessive amounts of protein to be in nutritional ketosis, but higher amounts of protein may be acceptable when exogenous MCT are provided. Described below are some studies with athletes consuming MCTs or ketogenic diets.

In cyclists who consumed beverages with 10% glucose and 4.3% MCT, muscle glycogen was spared, lactate was reduced, and time trials were completed more rapidly, versus cyclists who consumed only glucose or only MCT ^[35]. In another study, recreational cyclists who consumed foods containing 6 g MCT for two weeks had longer time to exhaustion at 80% peak VO₂ compared to those consuming equivalent amount of longer chain fats ^[36]. This indicates MCTs will have a performance benefit. Ketones are not currently on WADAs prohibited substance or monitoring list, but are apparently already being used by professional cyclists to improve performance ^[37], and being used by Team Sky (but they will not confirm so as to keep their competitive advantage!).

Women artistic gymnasts who consumed a very low carbohydrate modified ketogenic diet for 30 days, there was no loss in athletic performance, but body weight and fat mass decreased, with a non-significant increase in muscle mass ^{[38, 39]}. Since the majority of athletes struggle to keep their weight down living in our land of plenty, these results are encouraging, particularly for weekend warriors. Boxers, weight lifters, wrestlers, etc. could also benefit from an MCT diet.

In Taekwondo karate athletes, athletes lost similar body weight and body fat on both ketogenic (high fat foods) and non-ketogenic diets, but the ketogenic diet improved measures of athletic performance (finished 2,000 m sprint in less time and felt less fatigue in the Wingate test) and reduced measures of inflammation relative to the non-ketogenic diet ^{[40, 41]}. Ketone bodies are known to have anti-inflammatory properties, and this is yet another advantage of consuming the combination of MCTs and KBs.

In murine swimmers (swimming mice), MCTs increased endurance swim capacity, relative to mice who consumed longer chain fatty acid triglycerides, whether they were trained or not; and the mechanism likely involved improved mitochondrial TCA enzymes ^[42]. Let’s hope the same benefit applies to their human counterparts!

Diabetes: MCTs may benefit both type I and type II diabetes, by improving insulin resistance, improving hypoglycemic unawareness and associated cognitive measures, and diminishing glycogenolysis and glucose dumping into the plasma ^[43]. It is likely that insulin intake can be diminished and that a steadier blood sugar may result. In diabetes, cancer, and other diseases, the anti-oxidant benefits of KBs (decreased free radicals, increased glutathione peroxidase) are also important clinically ^{[8, 44]}.

Cancer: In 1914, Nobel Laureate Payton Rous, Father of the tumor virus, suggested restricted food intake reduced tumor growth by reducing tumor blood supply ^[45]. In 1924, the Nobel Laureate Otto Heinrich Warburg, determined that cancer cells have a dependency on glucose for growth and metastastic processes under hypoxic (low oxygen conditions), using glycolysis ^[46]. This physiological adaptation is called the “Warburg Effect”. Providing ketogenic diets and MCTs is a means to provide energy to normal cells, but restrict cancer cells form obtaining the glucose they need for their survival and metastasis (spreading). There is thus intense interest to evaluate the benefits of MCTs and ketogenic diets for combatting cancer ^[47-50].

Acne and skin inflammation: As high carbohydrate-diets can contribute to oxidative stress and inflammation under some conditions, it is even postulated that MCTs and ketogenic diets could improve conditions such as acne ^[51]!

References:

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