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).
This may have been mentioned, I haven’t checked all comments, but glutamine causes gluconeogenesis so that may explain why it affects Ketosis. Whenever I took a glutamine powder supplement for gut healing, I noticed I would “feel” less Ketogenic and I knew it was affecting me adversely. Glycine (which is also in bone broth) also has this effect I believe. Apparently some amino acids are just more easily converted to glucose.
For anyone who wants to get a bit more technical, research by Stubbs and colleagues shows that BHB shuts off lipolysis (fat breakdown). With endogenous ketosis there are many other factors that stimulate lipolysis meaning that a kind of balance is reached and lipolysis stays constant. But with exogenous ketosis those factors stimulating ketosis are not present, so the overall effect of the ingested BHB is to decrease lipolysis.
Before the Nobel Prize was awarded to Yoshinori Ohsumi, other researchers were making groundbreaking discoveries about autophagy. In 2009, an article was published in Cell Metabolism entitled Autophagy Is Required to Maintain Muscle Mass. In this article, researchers described how deactivating an important autophagy gene resulted in a profound loss in muscle mass and strength.
We designed a test for each of the chosen benefit claims and enlisted the help of four of our Diet Doctor teammates to try out the supplements and go through the testing. They were Jonatan and Giorgos from the video team, Emőke from the recipe team and Erik from the IT team. We had a mix of people who were naturally in endogenous ketosis during testing, and people who were not.
Patrick Arnold is an organic chemist who is notorious for being the creator of several performance-enhancing steroids. He is arguably one of the strongest influencers on the advancement of sports supplementation. Currently he is focused on developing products under the KetoSports brand, which includes two exogenous ketone products – KetoForce and KetoCaNa.
Here we investigated the effects of KE and KS consumption on blood βHB and metabolite concentrations. As we found that KE ingestion delivered a >50% higher plasma concentrations of d-βHB alone, we subsequently determined the reliability and repeatability of ketosis following KE consumption and the effects of concomitant meal ingestion on blood ketone and substrate kinetics. Finally, we determined whether nasogastric infusion could be used for KE administration, given that some patients require feeding in this manner.
There are enticing anecdotes of supplemental ketones being used to boost human physical performance in competitive events, notably among elite cyclists. Given that BOHB can deliver more energy per unit of oxygen consumed than either glucose or fatty acids (Sato 1995, Cox 2016, Murray 2016), this makes sense. But what we do not know is if there is any required period of adaptation to the use of exogenous ketones, and thus how to employ them in training. It is clear that exogenous ketones decrease adipose tissue lipolysis and availability of fatty acids, the exact opposite to what happens on a well formulated ketogenic diet. This distinction between exogenous ketones and ketogenic diets on adipose tissue physiology and human energy balance underscores an important reason why these two ketone-boosting strategies should not be conflated.
There are several ways to approach the “intermittent” part of food restriction. One of the most common is limiting the window in which food is consumed to about eight hours a day. Another is fasting for a full 24 hours once a week, or once a month. Fasting beyond three days can be stressful on the body and should be done with medical advice and supervision.
Second, there are inherent metabolic differences between boosting ketones via diet and boosting ketones via supplements. On a ketogenic diet, ketones go up because you’re converting body and dietary fat into ketone bodies. A rise in endogenous ketones means you’re burning fat and building the requisite machinery to metabolize the new energy source. On exogenous ketones, ketones go up because you ate some ketones; conversion of body and dietary fat into ketone bodies goes down if anything.
Hi! I have what might be a silly question about using these supplements. What happens if you are taking them and your diet goes off the rails, like you take the Keto//OS and then eat a bunch of pizza or chocolate. Does your body just immediately revert back to using the carbs for energy instead of the ketones? Or, if it doesn’t, would that mean your body would just store those carbs as fat? I realize that ideally you wouldn’t eat the pizza, but sometimes I do and I worry about what exactly I’m doing to my body if I’ve also taken ketones.
Intermittent fasting is using the same reasoning – instead of using the fats we are eating to gain energy, we are using our stored fat. That being said, you might think it’s great – you can just fast and lose more weight. You have to take into account that later on, you will need to eat extra fat in order to hit your daily macros (the most important thing). If you’re overeating on fats here, you will store the excess.
Is keto safe? Putting yourself through this type of therapy isn't always easy and the process can take some getting used to, in particular during the initial stages when people must go through a period of fasting in order to raise ketone bodies faster. Of course, by doing this, it can put your body through a bit of shock and may cause a person to experience some short-term side effects until their bodies begin to adapt to the lifestyle and any BHB supplement they may be taking.
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.
An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017), in three extremely ill pediatric patients (Plecko et al., 2002; Van Hove et al., 2003; Valayannopoulos et al., 2011) and in cyclists (O'Malley et al., 2017; Rodger et al., 2017). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis. Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, d-βHB, and l-βHB, despite the metabolism of l-βHB being poorly understood (Webber and Edmond, 1977; Scofield et al., 1982; Lincoln et al., 1987; Desrochers et al., 1992). The pharmacokinetics and pharmacodynamics of KS ingestion in healthy humans at rest have not been reported.
BHB Salts and exogenous ketone supplements are literally changing the supplement industry. These products are pretty new and a little more expensive than other supplements. But I’d rather pay for something that works then spend tons of money chasing products that claim to work. One of the most popular ketone supplements is Pruvit’s Keto OS. You can check out our review here.
I heard a rep from Perfect Keto on a podcast and your Exogenous Ketones. I ordered and received it the other day. I see from this article that I should not do a full scoop at once, but break it up in a day. Good to know. I had about a half scoop before I worked out this morning and could tell I had more energy. Loved that. Just curious….any ideas how long it will take me to get back into ketosis and fat burning?? (I know it depends on what I eat, but a general idea that I promise not to hold you too! (I’m actually missing having ‘keto breath!)
In a keto-adapted individual where ketone metabolism is brisk with up to 100 grams or more being oxidized (i.e., ‘burned for energy’) daily, the small amount lost in breath and urine as acetone is minor. But because this breakdown occurs spontaneously without needing the help of enzymes, it also happens to AcAc in a stored beverage or food (even in an air-tight container), making the shelf-life of AcAc-containing products problematic. Thus all current ketone supplements consist of BOHB in some form rather than the naturally occurring mix of BOHB and AcAc produced by the liver.
Also, this experiement should be of interest. Two men followed a ‘traditional Eskimo’ diet for 1 year. After the year eating a low carb high fat diet, it was found that the men had a diminished tolerance to carbohydrates, something that did not occur in Eskimos eating the same diet. It took the mean nearly a month of eating a ‘normal diet’ before their glucose tolerance returned to baseline.
On day 29, rats were sacrificed via deep isoflurane anesthesia, exsanguination by cardiac puncture, and decapitation 4–8 h after intragastric gavage, which correlated to the time range where the most significantly elevated blood βHB levels were observed. Brain, lungs, liver, kidneys, spleen and heart were harvested, weighed (AWS-1000 1 kg portable digital scale (AWS, Charleston, SC)), and flash-frozen in liquid nitrogen or preserved in 4 % paraformaldehyde for future analysis.
As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
Her clients have had similar success. One woman, for instance, has gone from around 170 pounds to 140 pounds since April without making any initial dietary changes. She’s started to gravitate towards more keto foods over time, but still eats her favorite high-carb treats. As for exercise? Her routine consists of a couple of walks each week, Heverly says.
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...
Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.
Response inhibition is the ability to suppress inappropriate responses that interfere with goal-directed actions. Two cards are shown, one above the other, each containing the name of a color in a certain color. The goal is to rapidly indicate if the meaning of the color on top (i.e. “yellow”) matches the color of the color on the bottom (i.e., card says “red” but is colored yellow).
Directions — — As a dietary supplement, mix 1 scoop of ketone powder with 8-12 oz of water To avoid gastrointestinal discomfort, start with 1/2 scoop (or even less) and gradually increase to a full serving. Best consumed prior to exercise to enhance performance. Do not exceed 3 scoops per day. As a dietary supplement take 1 serving of PX Ketotropin twice daily. Ideally the 1st servings (4 capsules) should be taken prior to the first meal of the day. Consume 2nd serving 30 minutes prior to strenuous physical activity. If no physical activity is performed please consumer 2nd serving prior to afternoon meal. Additional servings can be taken in between meals throughout the day if needed. Do not consume more than 6 servings of PX Ketotropin
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