I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
Beta hydroxybutyrate floats around in your blood, and importantly, can cross different barriers to be able to be turned into energy at all times. One of the most important areas where this happens is in the brain. The blood-brain barrier (BBB) is usually a very tightly regulated interface that doesn’t allow the transfer of many molecules, but since BHB is such a rock star and so hydrophilic, your brain knows to let it in so it can bring energy to the party at any time. This is one of the main reasons why increased levels of ketosis lead to improved mental clarity, focus and reduction in neurodegenerative diseases.
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
If you have tried other ketone supplements that haven’t worked as promised or tasted terrible. Have no fear. This stuff is what a ketone supplement should be. It’s incredible what customers tell me. How it’s given them more energy, focus, drive. Helped them lose weight and suppress their appetite. Help them train harder at the gym and all kinds of great stories.*
So long long does it take to get into ketosis? This transition could take anywhere from 48 hours to one week. The length in time will vary depending upon your activity level, lifestyle, body type and carbohydrate intake. There are several ways you can speed up this process, like intermittent fasting, drastically decreasing your carb intake and supplementation.
Calories do matter, even on a ketogenic diet. If you consume more calories than your body uses, you’re going to gain weight. Period. What you mean to say is that it’s very difficult to eat your entire day’s worth of calories on a ketogenic diet because fats are so satiating. This distinction is important to keep in mind for those who generally have a voracious appetite (like me).
For the past few million years, the only way for humans to make use of ketones for fuel was to restrict carbohydrates low enough and long enough to induce the liver to make them. This is admittedly hard for many people to do in a world that still believes that dietary carbs are good and fats are bad. An emerging alternative is to consume ketones as a dietary supplement. The research into how these function in the body and what benefits they can confer remains early stage, but there are already a number of such products available for sale. In this section, we will discuss how exogenous ketones affect blood ketone levels, and how they may influence health and disease compared to ketones produced within the body.
Participants consumed 13.2 mmol.kg−1 of βHB (6.6 mmol.kg−1 or 1,161 mg/kg of KE) over 9 h, either as 3 drinks of 4.4 mmol.kg−1 of βHB at 3 h intervals (n = 12), or as an initial bolus of 4.4 mmol.kg−1 of βHB given through a nasogastric tube, followed by an infusion of 1.1 mmol.kg.h−1, beginning 60 min after the initial bolus, for 8 h (n = 4). Two participants completed both conditions (total n = 14). In both conditions, the KE was diluted to 1.5 L using the same citrus water as used in Study 2.
The other potentially important distinction between nutritional ketosis and chemically-induced ketosis is the potential metabolic role played by liver AcAc production and redox status. Although the ratio of BOHB to AcAc in venous blood is typically 80% to 20%, classic studies by Cahill (1975) have observed important hepatic vein and peripheral arterio-venous gradients for this ratio in keto-adapted patients. What these observations imply is that the liver produces a higher proportion of AcAc than is found in the peripheral blood, and that this is due to uptake of AcAc in peripheral cells (principally muscle) with re-release as BOHB. In the process, the reduction of AcAc to BOHB produces NAD+, which is beneficial to mitochondrial redox state and mitochondrial function (Verdin 2015, Newman 2017).
When you are in a state of ketosis, the body turns fatty acids into ketones - these appear as beta-hydroxybutyrate in the blood. Measuring blood ketones is regarded as the gold standard and most accurate way to track ketone levels. Testing this way can be expensive, its can cost up to $3 a strip, so if you're testing multiple times a day it can get pricey.
Exogenous ketones have become a popular nutritional supplement since their introduction in 2014. Unfortunately there is a lot of inaccurate information and marketing you have to read through to find the truth about them. This article does the hard work for you. It gets right to the true benefits and drawbacks of exogenous ketones supported by research studies.
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.
Blood, urine, plasma, and breath ketone concentrations following mole-matched ketone ester or isocaloric dextrose drinks in fed and fasted subjects (n = 16) at rest. Data from both of the two study visits in each condition (fed and fasted) completed by an individual are included in the analysis. Values are means ± SEM. (A) Blood d-βHB. (B) AUC of blood d-βHB. (C) Urine d-βHB excretion. (D) Plasma acetoacetate (AcAc). (E) Measured breath acetone (ppm = parts per million). (F,G) Mean d-βHB Cmax and difference between βHB Cmax over two visits when subjects separately consumed two ketone ester drinks in both the fed (F) and fasted (G) state. X axis = mean d-βHB Cmax of the 2 visits (mM), Y axis = difference between d-βHB Cmax in each visit. 95% confidence limits are shown as dotted lines. Significance denoted by: *p < 0.05 fed vs. fasted.
Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below).
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.
However, it's important to NEVER overlook the power of exercise and of course sticking to a proper routine to get the most optimized results. The most common mistake people make is by treating any keto supplement like a "wonder drug" that will help them shred weight in their sleep. Seriously... how is that even scientifically possible. So if you are thinking about trying out a particular supplement, I would suggest two things:
If you have already mastered the Very Low Carbohydrate (VLC) or ketogenic way of eating, and/or are eating at a caloric deficit, exercising or fasting you are naturally creating the optimal conditions for your body to produce ketones and put your body into nutritional ketosis. By strict adherence to a well-formulated ketogenic diet (complete with higher levels of mineral salts) you should be able to produce all the ketones you need naturally (endogenously). If you are new or inexperienced in ketogenic eating however; or if you or a family member struggles to adhere to a ketogenic diet, then supplementation with exogenous ketones may be very beneficial. Not only will ketone supplements help to mitigate hunger and carb cravings, but they will also help you stave off carb flu symptoms (see below), giving you the best possible chance of long-term success.
Hi Acadia, just want to clear up a few things you noted in your post: The manufacture of BHB salts involves ionic bonding of an anion (beta-hydroxybutyrate) with a cation (Na+, K+, Ca+, Mg+). At least one of the exogenous ketone products you listed does in fact contain potassium ions. People taking potassium-sparing drugs need to know this and that raises concerns about leaving it off your chart. Some people are genuinely sodium sensitive even to small amounts of salt added to otherwise healthy foods. This can hold true even for those following ketogenic diets. The term you’re looking for… Read more »
Ketone monoester and diester compounds may circumvent the problems associated with inorganic ion consumption in KS drinks. KE ingestion rapidly increased blood ketone concentrations to >5 mM in animals (Desrochers et al., 1995a,b; Clarke et al., 2012a) and the first oral, non-racemic KE for human consumption, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, raised blood βHB concentrations to 3–5 mM in healthy adults (Clarke et al., 2012b; Shivva et al., 2016) and athletes (Cox et al., 2016; Holdsworth et al., 2017; Vandoorne et al., 2017). However, the pharmacokinetics and pharmacodynamics of this KE with confounding factors, such as prandial state or multiple KE drinks, have not been characterized.
Exogenous ketones are becoming more popular as advancements in scientific research continue to show how they work to improve both health and performance. At first, the only options for delivering exogenous ketones were unpalatable ketone esters; however, exogenous ketones can now be taken in the form of ketone mineral salts that are more palatable and easily blended in water. Making ketone mineral salts involves combining beta-hydroxybutyrate (BHB) with mineral salts such as sodium, calcium, magnesium, or potassium. Before considering whether ketone supplements are a good option, most people immediately look at the salt load, and rightfully so. It is important to take into account the nutritional and health impact of not only the BHB but the minerals that are used to make the product.
*These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. Information on this site is provided for informational purposes only, it is not meant to substitute medical advice provided by your physician or any other medical professional. You should not use the information contained on this site for diagnosing or treating a health problem, disease, or prescribing any medication. Please read product label before use. Best results are only achieved when combined with diet and exercise program. Results not typical for any or all claims.
The USDA guidelines recommend less than 2400 mg of sodium per day for healthy adults, and 1500 mg or less for individuals over the age of 50 or at risk for hypertension. For reference, 2300 mg of sodium is the equivalent of about one teaspoon of salt. Even though these recommendations are promoted by the American Heart Associated and other health-related organizations, recent research has claimed that there is simply not enough evidence to support these guidelines. Worldwide 24-hour urinary sodium excretion data suggest that the normal range is actually 2500-5000 mg per day, which is what most of us consume daily. Additionally, people with high activity levels or chronically low blood pressure may require more sodium than the average person.
Ketosis supplements made in poor quality, have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men, and women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is really important to know what combination of compounds you are consuming, particularly while you are on this very strict diet because the wrong balance can really mess with you in the long term and won't give you the high performance that you are looking for.
Over the 28-day experiment, ketone supplements administered daily significantly elevated blood ketone levels without dietary restriction (Fig. 2a, b). Naturally derived ketogenic supplements including MCT (5 g/kg) elicited a significant rapid elevation in blood βHB within 30–60 min that was sustained for 8 h. BMS + MCT (5 g/kg) elicited a significant elevation in blood βHB at 4 h, which was no longer significant at 8 h. BMS (5 g/kg) did not elicit a significant elevation in blood βHB at any time point. For days 14–28, BMS + MCT (10 g/kg) and MCT (10 g/kg) elevated blood βHB levels within 30 min and remained significantly elevated for up to 12 h. We observed a delay in the peak elevation of blood βHB: BMS + MCT peaked at 8 h instead of at 4 h and MCT at 4 h instead of at 1 h. Blood βHB levels in the BMS group did not show significant elevation at any time point, even after dose escalation (Fig. 2a). Synthetically derived ketogenic supplements including KE and BD supplementation rapidly elevated blood βHB within 30 min and was sustained for 8 h. For the rats receiving ketone supplementation in the form of BD or the KE, dosage was kept at 5 g/kg to prevent adverse effects associated with hyperketonemia. The Precision Xtra™ ketone monitoring system measures βHB only; therefore, total blood ketone levels (βHB + AcAc) would be higher than measured. For each of these groups, the blood βHB profile remained consistent following daily ketone supplementation administration over the 4-week duration. (Fig. 2b).
Human's ability to produce and oxidize ketone bodies arguably evolved to enhance survival during starvation by providing an energy source for the brain and slowing the breakdown of carbohydrate and protein stores (Owen et al., 1967; Sato et al., 1995; Marshall, 2010). The brain is normally reliant on carbohydrate as a substrate, being less able to metabolize lipids, despite adipose tissue representing a far larger energy store than muscle and liver glycogen. Therefore, during starvation, lipids are used for hepatic ketogenesis and, via ketone bodies, lipids sustain the brain. Endogenous production of the ketone bodies, d-β-hydroxybutyrate (βHB) and acetoacetate (AcAc), increases slowly, driven by interactions between macronutrient availability (i.e., low glucose and high free fatty acids) and hormonal signaling (i.e., low insulin, high glucagon and cortisol). Produced continuously under physiological conditions, blood ketone concentrations increase during starvation (Cahill, 1970), when consuming a “ketogenic” (low carbohydrate, high-fat) diet (Gilbert et al., 2000) or following prolonged exercise (Koeslag et al., 1980).
Price: The supplements are expensive – very expensive. At the top end, if you follow Prüvit’s guidelines on “getting in the n8tive zone” (which is such a gimmicky marketing slogan it almost makes me cringe), you will require 2 servings of their Keto-OS product per day. This means around 60 servings per month, which will set you back a whopping $390 per month if you buy direct from their website! In the case of Prüvit, this is in part due to the multi-level marketing structure they operate under.
I’m already following a ketogenic diet and have been fat adapted for about 3 months. Since I’m already in ketosis would this product help me or hinder my fat loss? My thought is that if I’m already in a fat burning state and then I take exogenous ketones does my body stop burning my fat to burn the ingested ketones like taking a break or does the product enhance the fat burning that is already taking place?
Meanwhile Brinkworth, et al., in their 2009 paper "Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function" looked at the effects on ketogenic diet on cognitive function and mood. The study participants ate a ketogenic diet for a year and the researchers found that mood levels decreased when compared to a group eating a high carb/low fat diet. They go on to remark “there was no evidence that the dietary macronutrient composition of LC and LF diets affected cognitive functioning over the long term, as changes in cognitive function were similar for both diets”.
Today, 4/27, I received the Peaches & Cream. I was reluctant to purchase, but I didn't want to wait until Saturday for the Salted Chocolate. After dinner, I mixed it in water, added heavy cream, put it over ice. Delicious!!! I believe these products work bc I can still eat up to 50-100g of carbs on a lax day and still drop weight since it keeps me in Ketosis.
The ketone esters are, hands-down, the worst tasting compounds I have ever put in my body. The world’s worst scotch tastes like spring water compared to these things. The first time I tried 50 mL of BHB monoester, I failed to mix it with anything (Dom warned me, but I was too eager to try them to actually read his instructions). Strategic error. It tasted as I imagine jet fuel would taste. I thought I was going to go blind. I didn’t stop gagging for 10 minutes. (I did this before an early morning bike ride, and I was gagging so loudly in the kitchen that I woke up my wife, who was still sleeping in our bedroom.) The taste of the AcAc di-ester is at least masked by the fact that Dom was able to put it into capsules. But they are still categorically horrible. The salts are definitely better, but despite experimenting with them for months, I was unable to consistently ingest them without experiencing GI side-effects; often I was fine, but enough times I was not, which left me concluding that I still needed to work out the kinks. From my discussions with others using the BHB salts, it seems I have a particularly sensitive GI system.
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