If the claims about the benefits of exogenous ketones are accurate and true, then it’s fantastic news for people who are looking to enhance their keto lifestyle and who have the money to spend. But two of our core values are trustworthiness and goodness, and it is important to us to test assumptions made by marketing claims and help make sure that people are getting what they are told they are getting when they spend money on a product.
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At baseline, 4 h after intragastric gavage, the elevation of blood ketones was inversely related to the reduction of blood glucose compared to controls following the administration of MCT (5 g/kg) (p = 0.008) and BMS + MCT (5 g/kg) (p = 0.039) . There was no significant correlation between blood ketone levels and blood glucose levels compared to controls for any other ketone supplemented group at baseline (Fig. 4a). At week 4, 4 h after intragastric gavage, there was a significant correlation between blood ketone levels and blood glucose levels compared to controls in MCT (10 g/kg) and BMS + MCT (10 g/kg) (p < 0.0001, p < 0.0001) (Fig. 4b).
Relationship between blood ketone and glucose levels: a BMS + MCT (5 g/kg) supplemented rats demonstrated a significant inverse relationship between elevated blood ketone levels and decreased blood ketone levels (r2 = 0.4314, p = 0.0203). b At week 4, BMS + MCT (10 g/kg) and MCT (10 g/kg) showed a significant correlation between blood ketone levels and blood glucose levels (r2 = 0.8619, p < 0.0001; r2 = 0.6365, p = 0.0057). Linear regression analysis, results considered significant if p < 0.05
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 “BHB salt” is simply a compound that consists of sodium (Na+), potassium (K+), and the ketone body β-hydroxybutyrate. In supplements like Pruvit’s Keto OS these individual components are being held together by ionic bonds; however, when you consume the product, it is absorbed into the blood where it dissociates into free Na+, K+, and BHB since it is a water-based solution. Thus, consuming the product directly and immediately puts more ketones into your blood.
That said, there also remains the question of the relative benefits of AcAc versus BOHB, both as independent signaling molecules and as redox modulators in peripheral (aka non-hepatic) tissues. Seen from this perspective, AcAc generated in the liver acts as a NAD+ donor for the periphery, whereas pure BOHB taken orally, to the extent that it is retro-converted to AcAc (Sherwin 1975), potentially deprives the periphery of NAD+.
I came across a new company called KetoneAid that has begun producing small batches of ketone monoesters (KMEs). The main molecule in their product (D-β-hydroxybutyrate / D 1,3-butanediol) is based on a five-year, $10M study commissioned by the Defense Advanced Research Projects Agency (DARPA), looking to create the most powerful source of energy for special operations soldiers such as Navy SEALs, when undertaking very physically and cognitively challenging missions. In fact, the main researcher of the DARPA study is Dr. Richard Veech, the same person that authored the longevity study I just mentioned. Very cool.
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.
One other thing I must point out is also that we are talking about being in ketosis and not being fully keto adapted. You enter ketosis when your body starts producing ketones above a specified level, being fully keto adapted means that your body is full adapted to use fat as your primary energy source and that the production of certain enzymes in your body is fully adapted. This doesn’t happen in one day and it takes about 1 month on average to be fully keto adapted. But we are not looking for this as we just want to end the most unpleasant period and to start losing weight.
Individuals who have clinically unregulated blood sugar, such as those with diabetes, are cautioned to consult their trusted healthcare provider before choosing to use exogenous ketones. While it can be done safely, especially in the presence of a well-formulated ketogenic food plan, there may be a risk of blood sugar dropping unexpectedly low. There may be therapeutic value in this application, but close monitoring is key.
Intermittent fasting involves merely changing your eating cycle whereby you prolong the period in which you will have your first meal. This diet plan helps to create a smaller eating window. In doing so, it means that you will consume less amount of calories. In addition to depriving the body some calories, intermittent fasting forces the body to begin burning fats. It does so to compensate for the current deficiency.
So if your high-fat diet includes a high amount of roasted seeds or roasted nuts, nut butters, heated oils such as heated coconut oil or heated extra virgin olive oil, barbecued meats or meats cooked at very high temperatures, then your triglyceride count is going to go up. You should have triglycerides that are less than 150mg/dL, and a triglyceride to HDL ratio that is no more than 4:1, and in most of the healthiest people I’ve worked with, triglycerides are under 100 and the triglyceride to HDL ratio is less than 2:1. If your ratio is whacked, your ketogenic diet isn’t doing you any favors.’
In a nutshell… WOW! The chart above shows each of the games/categories I played, showing my prior 5-day averages compared to the day I took the ketone esters. Compared to my baselines, my scores increased across the board, with the biggest improvements in spatial orientation (+32.2%), working memory (+23.7%), quantitative reasoning (21.5%), task switching (+14.9%), and information processing (+14.9%). Below are more detailed comparisons:
I began by simply playing all of the games over and over again (each game many dozens of times over the period of a week) to remove any “learning effect.” I then selected two games from each category (for a total of 10 games) and for a period of five days prior to “ketone-day” played each game five times each day. My “before ketones” baseline scores put me in the top 4% of all Lumosity users, so I was already in a good place. But could I improve even more, just one hour after consuming the ketones?
It might sound absolutely crazy to go that long without food. Especially when you consider traditional diets that recommend eating 3-5 small meals each day, starting with breakfast – the “most important” meal of the day. But if you think back to hunter gatherer times, human beings didn’t always have food accessible to us. Farming and agriculture hadn’t existed so our first meal each day would vary quite vastly. If you think about the word itself, ‘breakfast’ means to break-fast. We didn’t have a set time where we would consume our first meal – it was dependent on accessibility. So if you’re wondering how you’re going to survive without going for food for 16 hours, the answer is straight forward – you can! Let’s simplify this and break down what this may potentially look like.
Some general side effects of your body producing beta hydroxybutyrate is essentially the lull in time it takes to switch from carbohydrate metabolism to fat metabolism, which can take 3-4 days. This can lead to mood swings, fatigue, and general low energy. If you want to skip that step, we recommend taking exogenous BHBs to switch your body over effortlessly.
We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
Exogenous ketones are ketones that come in the form of a powder that you mix with water to drink them. Exogenous ketones are controversial in the keto world. The problem is the marketing of them have made some people believe that all they have to do is use this product to get into ketosis. If your blood glucose is too high your body will not use the ketones and they will go to waste.
Hello! We have a section on this in our weight loss plateau post—it’s fine to use them, but be careful if you have any digestive issues as a result of them, and make sure they’re not interfering with your weight loss goals. “In addition to potentially contributing too many calories, sources of fat like coconut oil (including concentrated supplements) contain medium chain triglycerides (MCT). These cannot be stored in body fat, meaning that whatever is consumed has to be promptly burned for energy. So you’re adding these sources on top of your dietary fat consumption for satiety, this type of fat takes priority. Often times people fall into the trap of adding supplements of coconut oil or straight up MCT oil and it ends up adding extra calories. Yes, it may raise your ketones a bit, but the overall cost may impact your weight loss.”
If you stop eating carbs, your body first uses up glucose reserves stored in the liver and muscles. After it burns all that's left of glucose, it has no other options but to start burning fat. It can burn either your body's fat stores or the fat you eat. However, not all cells in your body can use fat to make energy and this is where ketones come into play.
Getting into a state of ketosis normally involves eating a ketogenic diet consisting of around 80 percent fat, 15 percent protein, and 5 percent carbs. Over time, the body transitions from burning carbs for fuel to burning ketones—an alternative fuel source that the liver makes by breaking down fat, explains keto diet expert Amy Davis, RD, LDN. Since advocates say that ketosis can help you lose weight fast, think more clearly, and feel more energized, it’s tempting to try.
d-βHB was measured immediately on whole blood using a handheld monitor and enzyme-based reagent strips (Precision Xtra, Abbott Diabetes Care, UK). Samples were stored on ice, centrifuged and duplicate plasma aliquots stored at −80°C. All urine passed during the visit was collected, the total volume recorded, and 1 ml aliquots taken, frozen and retained for analysis.
I had heard horror stories about how bad ketone esters tasted (like “rocket fuel”!) so was prepared for the worst. I followed their instructions and drank the contents of the bottle in one gulp, then chased it with a sip of sparkling mineral water. While not the most pleasant aftertaste, the flavor wasn’t any worse than after a shot of well tequila. Within 15 minutes I was already well into therapeutic ketosis, and after 30 minutes my ketone meter displayed a “HI” error message (meaning my level was greater than 8.0 mmol/L)!
All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.
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