BS, KC, and PC designed the research studies. BS, PC, RE, SM, and PS carried out the studies. SH provided the gas analyser used in the study on behalf of NTT DOCOMO Inc. BS, MS, and SM analyzed the data and performed statistical analysis in collaboration with JM. BS wrote the paper with help from KC, PC, and OF. KC had primary responsibility for final content. All authors read and approved the final manuscript.
Are you ready for a very basic metabolism overview? Most modern humans break down carbohydrates into glucose and this then breaks down further and enters mitochondria to produce ATP, which is the energy system of your cells. In other words, you use carbs for energy. When you are on a ketogenic diet, you are breaking down fats into things called ketone bodies, and this is how you provide your body with energy, instead of via carbohydrates. So, you’re either using carbohydrates for fuel or fat for fuel. 

But some people chose to use supplements to benefit from ketosis (Therapeutic Ketosis), and finally there is the MCT Ketogenic Diet – which in a form of nutritional ketosis (ULC, limited protein, high fat) with a twist – about 30-60% of the fat intake in the diet comes from MCT (Medium Chain Triglyceride) fats. Sources of MCT fats include Pure MCT Oil, Coconut oil and coconut products. The MCT Ketogenic Diet is often used with epilepsy suffers, as the high levels MCT oil create a higher level of ketones in the blood – which helps prevent seizures.
Because they’re so expensive, you want to make sure you pick a good one. Griffin and Langer say to ignore the companies that make these supplements sound too good to be true. Just like with any supplement, Griffin says it’s important to look at what’s in it. Beware of products with lots of fillers and instead go for one with a short, straightforward list of ingredients (Griffin likes the options from KetoSports).

Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...
As I mentioned before, this was by no means a scientific experiment carried out under lab conditions, and this means we can only draw tentative conclusions from any of the data. Nonetheless, carrying out the testing in the way described above should give most people a good idea of how well the ketone supplements show the noticeable benefits they are marketed to have and provide a clear enough basis for a decision on whether or not to buy them.
The chart below shows my ketone and glucose response to consuming 40g of KetoneAid’s ketone esters, which had been calculated to be my optimal serving size based on my weight (170lbs) and type of activity (I am moderately active/athletic, but cognitive experiments are a “low” physical activity). Normally, for increased physical performance ketone esters are consumed along with some glucose, but since I was only focusing on cognitive performance I did not consume any glucose.
Another factor to consider is that in nutritional ketosis the liver makes a steady supply of ketones and continuously releases them into the circulation. In contrast, most ketone supplement protocols involve bolus intakes that don’t mimic the endogenous release pattern. The extent to which this impacts metabolic and signaling responses across different tissues remains unclear.
The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.
How BHB turns into energy is a fairly simple process. As we’ve mentioned, beta hydroxybutryate eventually leads to energy production after you consume it or after your body breaks stored body fat down. It does this by going into the cell, entering the mitochondria (energy factories) at which stage it cleaves the carboxyl acid group and becomes acetoacetate (another “ketone body”). Acetoacetate turns into acetoacetyl-CoA, which then is cleaved to acetone (another “ketone body”) and acetyl-CoA. Acetyl-CoA is the whole reason we want BHB in the first place. This jumps into what is called the Kreb’s cycle (don’t you remember any of your biochemistry classes?) and is churned into ATP — the energy currency of your cells!
Instead of being bound to a mineral (like ketone salts), the ketone molecule (BHB or AcAc) is bound to a ketone precursor (e.g. butanediol or glycerol) via an ester bond. While there aren't as many esters on the market as salts, there is still some variance–especially when looking at the ketone molecule in these products. Before selecting the best one for you, it's important to gather all the necessary information to make your decision.
Exogenous ketones provide the body with another fuel to employ. Think about it like an electric car that runs on both gas and electricity: by consuming ketones along with carbohydrates, the body will preferentially burn the ketones first, saving the carbohydrates for later. Exogenous ketones allow us to enter a metabolic state that wouldn't occur naturally: the state of having full carbohydrate stores, as well as elevated ketones in the blood. This could be advantageous to athletes looking to boost their physical performance. 
A growing number of people are giving it a try, thanks to exogenous ketone supplements that claim to launch your body into a state of ketosis within two and a half days—even if you’ve been living on pasta and cookies instead of following a low-carb diet. How can that be, though? And can that kind of rapid transformation actually be safe? Here’s what you should know.
Hi, I still a little confused about when or how to take this. I am trying to get adapted and minimize the flu. Is it most beneficial before eating, after eating, with food or in place of food? I have been keto in the past but this time I am not switching over to fat burning mode even though my macros are good. ( I am thinking it is just too many calories and carbs at this point but I get hungry!) Help please.
Considering both the broad therapeutic potential and limitations of the KD, an oral exogenous ketone supplement capable of inducing sustained therapeutic ketosis without the need for dietary restriction would serve as a practical alternative. Several natural and synthetic ketone supplements capable of inducing nutritional ketosis have been identified. Desrochers et al. elevated ketone bodies in the blood of pigs (>0.5 mM) using exogenous ketone supplements: (R, S)-1,3 butanediol and (R, S)-1,3 butanediol-acetoacetate monoesters and diester [48]. In 2012, Clarke et al. demonstrated the safety and efficacy of chronic oral administration of a ketone monoester of R-βHB in rats and humans [49, 50]. Subjects maintained elevated blood ketones without dietary restriction and experienced little to no adverse side effects, demonstrating the potential to circumvent the restrictive diet typically needed to achieve therapeutic ketosis. We hypothesized that exogenous ketone supplements could produce sustained hyperketonemia (>0.5 mM) without dietary restriction and without negatively influencing metabolic biomarkers, such as blood glucose, total cholesterol, HDL, LDL, and triglycerides. Thus, we measured these biomarkers during a 28-day administration of the following ketone supplements in rats: naturally-derived ketogenic supplements included medium chain triglyceride oil (MCT), sodium/potassium -βHB mineral salt (BMS), and sodium/potassium -βHB mineral salt + medium chain triglyceride oil 1:1 mixture (BMS + MCT) and synthetically produced ketogenic supplements included 1, 3-butanediol (BD), 1, 3-butanediol acetoacetate diester/ ketone ester (KE).
This research is a good reminder to discuss with your doctor before taking any supplements. Given the widespread use of calcium supplements, more research is required before any final conclusions can be drawn. Several ketone companies have tried to avoid the large sodium loads but instead relied on a bump in the calcium content from the BHB ketone salts, seemingly without consideration for the aforementioned results. Calcium BHB will likely absorb slower compared to sodium BHB due to digestion and absorption kinetics.  For those looking to optimize brain uptake of ketones, this probably isn’t the best strategy (as uptake is directly proportional to the levels in the blood).   Be cautious of supplements running from the sodium and chasing the calcium BHB instead, and make sure you factor that into your overall daily needs.
Another effect of the ketone drinks was to lower blood glucose, free fatty acids, and triglyceride levels. This sounds great. Elevated levels of all those markers are harbingers of disease, particularly if they remain chronically elevated. But think about what this means. If free fatty acids go down, that means adipose tissue isn’t being liberated for burning.
Ketoacidosis is driven by a lack of insulin in the body.  Without insulin, blood sugar rises to high levels and stored fat streams from fat cells.  This excess amount of fat metabolism results in the production of abnormal quantities of ketones. The combination of high blood sugar and high ketone levels can upset the normal acid/base balance in the blood and become dangerous.  In order to reach a state of ketoacidosis, insulin levels must be so low that the regulation of blood sugar and fatty acid flow is impaired.
Again, there are very interesting animal studies plus some single case reports and small uncontrolled trials of humans with neurodegenerative disease and cancer given ketogenic diets and/or exogenous ketones (Murray 2016, Poff 2015, Roberts 2017, Newport 2015, Cunnane 2016). In some cases where the patient does not have the cognitive resources to comply with a well-formulated ketogenic diet, or where target blood levels of BOHB that work in animals are hard to achieve in humans by diet alone, supplemental ketones may have an important role to play in the prevention, management, or reversal of these disease categories.
Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...
The benefits of intermittent fasting translate to untrained overweight and obese individuals as well. One study published in Obesity Reviews found that eating fewer calories is effective for fat loss, but it does come with some muscle loss. However, if the subjects fasted for 24 hours and ate as much as they wanted on the next day for a period of 12 weeks, they lost significantly less muscle mass.
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Perfect Keto MCT Oil Powder is number one on this list for a few different reasons. The company is founded by functional medicine clinician Dr. Anthony Gustin and each ingredient is used in specific amounts to provide maximum ketone benefits. They use zero binders and fillers often found in other MCT oil powders. It’s a premium product and they don’t make up for it by jacking up the price. However, number 3 on this list has a very similar product at a better value. That’s what keeps this from being a complete 5. However, it’s quality is one of the very best. This MCT Oil powder is one of the only MCT powders that uses ZERO additives and fillers.
Spatial orientation (also known as sense of direction) involves being aware of the surrounding environment. The game involves navigating a penguin through a two-dimensional maze (up, down, left, right) to get to a fish. As the penguin moves through the maze, the entire screen periodically rotates to another orientation, so “up” for the penguin then becomes, say, “left” to the player, who must quickly adapt to the navigation controls.
Ketosis is a unique metabolic state where your body burns fat instead of glucose for fuel. Glucose is a simple sugar molecule derived from carbohydrates. Your body prefers using glucose to using fat and protein to make energy. This is because glucose it is easy to burn as it doesn't require much energy. On the other hand, your body uses fat and protein to build and repair tissue and make hormones.
Hypoglycemia: why not to be concerned – Taking exogenous ketones can drive blood glucose levels quite low, but you are not likely to feel the typical symptoms of hypoglycemia. This is because when ketone levels are high enough, they dominate as fuel in the brain; hence, you will feel just fine despite having low blood glucose. A highly-cited study by George Cahill, found elevated ketone levels could protect fasted participants when they were administered insulin to induce hypoglycemia.
Effects of ketone supplementation on organ weight: Data is represented as a percentage of organ weight to body weight. a, b, d, f Ketone supplements did not significantly affect the weight of the brain, lungs, kidneys or heart. c Liver weight was significantly increased as compared to body weight in response to administered MCT ketone supplement compared to control at the end of the study (day 29) (p < 0.001). e Rats supplemented with BMS + MCT, MCT, and BD had significantly smaller spleen percentage as compared to controls (p < 0.05, p < 0.001, p < 0.05). Two-Way ANOVA with Tukey’s post-hoc test; results considered significant if p < 0.05. Error bars represent mean (SD)

However, we will not be commenting on ketone esters since there are big differences between them and ketone salts, and the ketone salts are the ones that have been heavily commercialized and marketed to the public over recent years. Ketone esters may be more difficult to market due to their having an unpleasant taste. We may look more deeply into the esters in the future.


The final graph, below, shows the continuous data for only VO2 side-by-side for the 20 minute period. The upper (blue) line represents oxygen consumption under control conditions, while the lower line (red) represents oxygen consumption following the BHB ingestion. In theory, given that the same load was being overcome, and the same amount of mechanical work was being done, these lines should be identical.

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