These studies were approved by external Research Ethics Committees (London Queen's Square: 14/LO/0288 and South West Frenchay: 15/SW/0244) and were conducted in accordance with the Declaration of Helsinki (2008). Studies took place at the University of Oxford between September 2014 and September 2016. Participants were healthy, aged 21–57, non-smokers and had no history of major illness. Female participants were using oral contraception to minimize the effects of menstrual phase on results. Participants provided written informed consent prior to inclusion, and completed a confidential medical screening questionnaire to determine eligibility. Anthropometric characteristics are shown in Table Table1.1. Sample sizes were chosen following an estimated power calculation based on the effect size in previous work using KE drinks (Clarke et al., 2012b; Shivva et al., 2016).
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).
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
When our cells undergo the process of autophagy, non-essential parts like damaged proteins are recycled and invading microorganisms and toxic compounds are removed. This means that autophagy plays an important role in stopping the aging process, reversing disease, and preventing cancer, but it doesn’t happen all the time. Fasting, protein restriction, and carbohydrate restriction are the three main ways that can initiate different autophagic processes — all of which are not the same. This is part of the reason why a ketogenic diet has so many positive effects, and it also shows you why intermittent fasting is a way to improve your diet even 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.
This is delicious! I'm not sure what people are talking about when they say it tastes bad. I put a half scoop only (because its soooo expensive) in my iced coffee with have cream every morning and it tastes better than it ever did without. I'm not sure its really working and it does upset my stomach. I will have to get some strips to check ketosis and will come back to update. I think I'll probably still only give three stars though because it is WAY WAY WAY OVERPRICED! I can't believe how small the container was when it arrived for almost $60!! Even if it works, and it does taste delicious, I can't justify this kind of price point. This is such a bad business model. You probably get people to buy this once, maybe twice at this price, whereas if you made it more affordable, like double the product (an actual month's supply) you'd have customer's for life! Drop the price and I will buy again for sure!
In addition to the Weir coefficients being potentially off (which impacts EE), the RQ interpretation may be incorrect in the presence of endogenous or exogenous ketones. As a result, the estimation of fat and glucose oxidation may be off (though it’s directionally correct). That said, the current interpretation seems quite plausible—greater fat oxidation when I had to make my ketones; less when I got my ketones for “free.”
There are a couple factors that will make this look much more viable and achievable. For example, if you were to skip breakfast and have your first meal at 12PM, you could eat up until 8PM. This will also mean that dinner needs to be eaten slightly earlier. But let’s not forget about the fact that if we were to combine this with the 6-10 hours of sleep that you would normally have each night, that’ll take up the majority of your fasting period. Obviously, you’re not restricted to these hours, as everyone has a different schedule. Doesn’t sound as bad as you initially thought? Well let’s make it even more enticing! During your fasting hours, and this is extremely helpful during mornings up until you can have your first meal, non-caloric beverages such as tea and coffee can help starve away those hung pangs. Just make sure you’re taking these drinks on it’s own, without any added sugar or milk. There are many variations of intermittent fasting with the most common being 16/8. But depending on your schedule, there are other options advocated such as 20/4, 22/2, and if you’re crazy enough and can eat a full day’s worth of calories in one sitting then there is also OMAD (one meal a day).
If you are having a weight loss plateau and you’ve been at the same weight for 3 or more weeks, try changing something to get back to that stable weight loss rate, like a ketone supplement. It would be exciting to lose more than that each week, but our bodies don’t adjust to dramatic changes well, and a slower rate of loss leads to more of the weight staying off in the future.
Until there is more definitive information on the necessary blood levels and the differing proportions of BOHB an AcAc to optimize cellular and organ functions, it will be difficult to specify the dosing and duration of supplemental ketones. However for fuel use, and very likely for exercise performance as well, sustained blood levels of BOHB in the range of 0.5 mM to 1.0 mM are likely to be required. This is achieved physiologically by an estimated ketone production of 50-100 grams per day in a keto-adapted human.
Hi! My question is, how low must my current daily carb count be in order to benefit from taking your exogenous ketones? I am a 33 year old female, keeping total carbs at 100-125 grams per day. My priority is fat loss, and I do HIIT training 4-5 days a week. I’ll soon be adding in heavier strength training. I don’t function well eating less than 100 total carbs a day. Could this even benefit me? And if it will benefit me, would the befits outweigh the sodium content? I keep my sodium at 2,000 mg a day, as I’m trying to avoid water weight.
The protocols carried out in these studies were approved by the the South West Frenchay NHS REC (15/SW/0244) (Study 1) and London Queen's Square REC (14/LO/0288) (Study 2 and 3). The studies were carried out in accordance with the recommendations of the Declaration of Helsinki, apart from pre-registration in a database. All subjects gave written informed consent in accordance with the Declaration of Helsinki.
Blood d-βHB concentrations rapidly increased to a maximum of 2.8 ± 0.2 mM following the KE drink and to 1.0 ± 0.1 mM following the KS drink (Figure (Figure1A).1A). After the peak was reached, blood d-βHB disappearance was non-linear, and followed first order elimination kinetics as reported previously (Clarke et al., 2012b; Shivva et al., 2016). d-βHB Tmax was ~2-fold longer following KS drinks vs. KE drinks (p < 0.01, Figure Figure1B),1B), and KS d-βHB AUC was ~30–60% lower than the KE drink (p < 0.01, Figure Figure1C1C).
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).
I carried out a survey among Diet Doctor users as background research to the experiment (a big thank you to the 638 people who responded!). In the survey, 28% of the respondents reported that they do take ketone supplements. The top four benefits that these respondents reported experiencing were increased energy, improved focus/cognition, reduced hunger and weight loss.
I have tried the following preparations of exogenous ketones: BHB monoester, AcAc di-ester, BHB mineral salt (BHB combined with Na+, K+, and Ca2+). I have consumed these at different concentrations and in combination with different mixing agents, including MCT oil, pure caprylic acid (C8), branch-chained amino acids, and lemon juice (to lower the pH). I won’t go into the details of each, though, for the sake of time.
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