All data are presented as the mean ± standard deviation (SD). Data analysis was performed using GraphPad PRISM™ version 6.0a and IBM SPSS Statistics 22.0. Results were considered significant when p < 0.05. Triglyceride and lipoprotein profile data were analyzed using One-Way ANOVA. Blood ketone and blood glucose were compared to control at the applicable time points using a Two-Way ANOVA. Correlation between blood βHB and glucose levels in ketone supplemented rats was compared to controls using ANCOVA analysis. Organ and body weights were analyzed using One-Way ANOVA. Basal blood ketone and blood glucose levels were analyzed using Two-Way ANOVA. All mean comparisons were carried out using Tukey’s multiple comparisons post-hoc test.
Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.
Other studies have found that fasting was as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of chemotherapeutic drugs against melanoma, glioma, and breast cancer cells. Although this research may not apply to your life, it does suggest that intermittent fasting can help support your body in times of toxic stress.
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 . 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).
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).
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.
There are many different variations of intermittent fasting as well. Dr. Dom D’Agostino, the well-known ketogenic diet researcher, suggests doing a longer intermittent fast for 3 days, 3 times a year. This means not eating for 3 days, and eating normally until the next fast. Daily intermittent fasts are recommended as well. He says that it is ideal to have one to two meals after fasting for most of the day to reap the benefits of intermittent fasting every day.
It's important to listen to your body when going through the ketogenic process. This means that you should only eat when you're hungry and not every single time you get a craving. It's our obsession with food that causes us to stuff ourselves whenever we feel like it, and you should know by now that it's not healthy to do that. When you make it a point to eat only when you're hungry, you're diminishing any food intake that your body doesn't really need.
Those new to keto should be testing to see if their bodies are in ketosis, regardless of method. Testing, in general, is the most objective way to know if you’re in ketosis. There can be some subjective benefits of ketosis: appetite suppression, fat loss, low blood sugar, improvement in mental cognition and focus. But before recognizing these subjective benefits, it’s important to track and measure the level of ketones in the blood to ensure ketosis on a physical level.
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).
There are things you can do to get into ketosis faster. We explain how to get into ketosis and ways to make transitioning into ketosis easier. But first, we go over some facts about ketosis you need to understand before you start your keto journey. We will also explain the science behind ketosis, including how long it realistically takes for your body to make the switch.
Interest in the ketogenic diet is at an all-time high, and for good reason. It’s a great way to lose body fat, gain steady energy throughout the day, increase fat-burning capacity at rest and during exercise, reduce inflammation, and improve cognitive function. Keto also has a number of promising medical applications, including seizure control, enhanced efficacy of chemotherapy, and abatement of age-related cognitive impairment.
Anti-carcinogenic properties: Data seems to suggest that exogenous ketones are an effective anti-carcinogen. The reason behind this is that cancer cells are unable to use ketone bodies effectively, unlike most healthy tissues in the body. In fact, dietary ketone supplementation has been shown to increase survival rates of mice with systematic cancer by as much as 70%.17
BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells. With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.
*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 reason for testing after one hour was based on Prüvit’s “59-minute test”, which recommends testing ketones 45-60 minutes after taking the supplement (by the way, saying “59 minutes” instead of 60 minutes or 1 hour just sounds like another marketing gimmick to me). Kegenix Prime also promises “ketosis in 60 minutes” on its packaging. We carried out the testing at more or less the same time each day.
Weight loss benefits ushered the keto diet into the spotlight. That’s how most people have likely heard about ketones, a fuel source created naturally by the body when burning fat. But more and more research points to diverse applications of ketones in the blood outside of just fat loss, from improved endurance performance to the treatment of medical conditions like epilepsy.
77. Volek JS, Sharman MJ, Gomez AL, Scheett TP, Kraemer WJ. An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr. 2003;133(9):2756–61. [PubMed]
Intellectual property covering uses of dietary ketone and ketone ester supplementation is owned by BTG Ltd., the University of Oxford, the National Institute of Health and TΔS Ltd. Should royalties ever accrue from these patents, KC and PC, as inventors, will receive a share of the royalties under the terms prescribed by the University of Oxford. KC is a director of TΔS Ltd., a company spun out of the University of Oxford to develop and commercialize products based on the science of ketone bodies in human nutrition. At the time of data collection and manuscript preparation, BS was an employee of TΔS Ltd., funded by the Royal Commission for the Exhibition of 1851. SH is an employee of NTT DOCOMO, Inc. (Japan). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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
After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4
Ketogenesis is the metabolism of fatty acids by β-oxidation. 4 This process gives acetyl CoA which then leads to β-hydroxy-β-methyglutaryl-CoA (HMG-CoA) as seen below5. HMG-CoA converts into Acetoacetone which can switch back and forth to BHB. Acetoacetone to Acetone conversion is irreversible (on the left below). Acetoacetate and BHB (via acetoacetate) are used to produce energy when converted back into acetyl-CoA within a cell’s mitochondria whilst Acetone is excreted in the breath and urine.4
The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.
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I have Type 2 Diabetes. I have bought a product that has Beta Hydroxybutyrate in it. Is it dangerous for me to take it whereas I am a Type 2 diabetic. Can it cause me to go into Diabetic ketoacidosis which is very dangerous for a diabetic even deadly. I have been trying to find an answer to my question and your sight seems to have the best insight on Beta Hydroxybutyrate . I bought the product without knowing it had Beta Hydroxybutyrate in it and have not tried it out of fear that it will cause me to go into Diabetic ketoacidosis. Other people I know have taken it and lost weight and I really want to take it but I am afraid. Just so you know it is on a patch with other elements in it. Please help me I look forward to your answer
We carried out the testing across five different days, leaving at least two days between the different testing days so that my teammates had time to recover from the physical performance test each time. The reason we needed five days was that we included a placebo (an artificially flavored drink with no caffeine content) alongside the four brands we tested. Our teammates didn’t know that one of the supplements was a placebo. We also gave everyone a different supplement each time, to rule out any improvement in the tests being a result of people simply getting better at those tests over time.
 Shannon L. Kesl, corresponding author Angela M. Poff, Nathan P. Ward, Tina N. Fiorelli, Csilla Ari, Ashley J. Van Putten, Jacob W. Sherwood, Patrick Arnold, and Dominic P. D’Agostino (2016). Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutrition & Metabolism, 13(9)
Miriam, Thank you for the questions. I am going to do my best here to provide you with answers: Q: 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. A: The table lists the BHB and the mineral content from the BHB salts (no added minerals). Therefore, since potassium BHB is not in any of the… Read more »
Serial drinks or a continuous NG infusion of KE effectively kept blood ketone concentrations >1 mM for 9 h (Figure (Figure6).6). With drinks every 3 h, blood d-βHB rose and then fell, but had not returned to baseline (~ 0.1 mM) when the next drink was consumed. There was no significant difference in d-βHB Cmax between drinks 2 and 3 (3.4 ± 0.2 mM vs. 3.8 ± 0.2 mM p = 0.3), as the rate of d-βHB appearance fell slightly with successive drinks (0.07 ± 0.01 mmol.min−1 and 0.06 ± 0.01 mmol.min−1 p = 0.6). d-βHB elimination was the same after each bolus (142 ± 37 mmol.min, 127 ± 45 mmol.min; and 122 ± 54 mmol.min). When KE was given via a nasogastric tube, the initial bolus raised blood d-βHB to 2.9 ± 0.5 mM after 1 h, thereafter continuous infusion maintained blood d-βHB between 2–3 mM. Total d-βHB appearance in the blood was identical for both methods of administration (Serial drinks AUC: 1,394 ± 64 mmol.min; NG infusion AUC: 1,305 ± 143 mmol.min. p = 0.6).
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).
These statements have not been evaluated by the Food and Drug Administration. The content of this website is not intended for the treatment or prevention of disease, nor as a substitute for medical treatment or medical advice. Use of recommendations is at the choice and risk of the reader. If you are under medical supervision or taking prescription medications, please consult with your family doctor or medical provider before starting any new eating plan. Ketologie products are not intended to treat, cure or prevent any disease. Pregnant or breast feeding women should consult their health care professional before consuming.
Yes — you read that correctly — 24 hours of intermittent fasting without any resistance training and these subjects were able to preserve more muscle mass than the subjects that ate fewer calories every day without fasting at all. This finding contradicts our common sense, but when we dig deeper into autophagy we can find the mechanism behind this result.
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.
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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