This is another point that Brianna Stubbs put me onto: often, ketone-salt companies use terms such as “technology developed by Dominic D’Agostino” as a tool to market their products. Dom D’Agostino holds the patent for the technology being used but is not associated with the products and does not necessarily promote them. In many cases, this feels like a marketing strategy that name-drops a famous keto expert in order to make a product sound more legitimate. There is an example of this on Real Ketones’ website.
Thank you, Mark! I am an ME/CFS patient, and I have improved quite a bit on a ketogenic diet, which I have been following for the past 3 months. I am slowly losing weight (much needed) and I wondered, does using exogenous ketones inhibit fat loss? I’m trying to balance the benefits of continuing weight loss with benefits in dealing with ME/CFS symptoms. Thank you for any info you can offer!
For subjects completing the initial experiment (n = 15), the amount of d-βHB excreted in the urine increased with d-βHB intake, but was <1.5% of the total βHB ingested and was not different between matched doses of KE vs. KS (Figure ​(Figure1I).1I). There was no change in urine volume produced in different study conditions. Baseline urinary pH (5.7 ± 0.1) was unchanged by KE ingestion (pH 6.4 ± 0.2. p = 0.8 vs. baseline) but was significantly alkalinized by KS consumption (pH 8.5 ± 0.1. p < 0.001 vs. baseline) (Figure ​(Figure1J1J).
Recent studies suggest that many of the benefits of the KD are due to the effects of ketone body metabolism. Interestingly, in studies on T2D patients, improved glycemic control, improved lipid markers, and retraction of insulin and other medications occurred before weight loss became significant. Both βHB and AcAc have been shown to decrease mitochondrial reactive oxygen species (ROS) production [36–39]. Veech et al. have summarized the potential therapeutic uses for ketone bodies [28, 40]. They have demonstrated that exogenous ketones favorably alter mitochondrial bioenergetics to reduce the mitochondrial NAD couple, oxidize the co-enzyme Q, and increase the ΔG’ (free enthalpy) of ATP hydrolysis [41]. Ketone bodies have been shown to increase the hydraulic efficiency of the heart by 28 %, simultaneously decreasing oxygen consumption while increasing ATP production [42]. Thus, elevated ketone bodies increase metabolic efficiency and as a consequence, reduce superoxide production and increase reduced glutathione [28]. Sullivan et al. demonstrated that mice fed a KD for 10–12 days showed increased hippocampal uncoupling proteins, indicative of decreased mitochondrial-produced ROS [43]. Bough et al. showed an increase of mitochondrial biogenesis in rats maintained on a KD for 4–6 weeks [44, 45]. Recently, Shimazu et al. reported that βHB is an exogenous and specific inhibitor of class I histone deacetylases (HDACs), which confers protection against oxidative stress [38]. Ketone bodies have also been shown to suppress inflammation by decreasing the inflammatory markers TNF-a, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46, 47]. Therefore, it is thought that ketone bodies themselves confer many of the benefits associated with the KD.
Over the years, we have seen and heard many different things about the effects and benefits of Raspberry Ketone supplements. Be it capsules or sprays, the discussion around them actually working always had opposing sides. So, we decided the best solution was to do our own research by conducting our own reviews on the most talked about products, to find out exactly how good they were as a "top-rated" ketone supplement.

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).

When you restrict carbs, the kidneys excrete a lot of sodium. Not replacing this sodium can leave you feeling light headed. I recommend having a big glass of spring water with ½ teaspoon of Celtic sea salt twice a day (first thing in the morning and midafternoon are two times that work well). A long with this, make sure you use a lot of salt on your meals.
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.
The blood levels of BOHB that can be achieved with the salts or ester formulations are in the 1-3 mM range, similar to what can be achieved with a well-formulated ketogenic diet in insulin sensitive humans, but well below levels achieved after a 4-7 days of total fasting (Owen 1969). In more insulin resistant humans, the ester formulation may deliver higher blood levels than a sustainable diet (as opposed to short term fasting). For example, in the Virta IUH Study of over 200 patients with type 2 diabetes, blood ketone mean levels were 0.6 mM at 10 weeks and 0.4 mM after 1 year.
The CNS cannot use fat as an energy source; hence, it normally utilizes glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources, and as demonstrated by the classic experiments of Cahill and colleagues4 this alternative energy source is derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies (KBs), that is, acetoacetate, β-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs principally in the mitochondrial matrix in the liver.6
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.
Exogenous ketones have a wide range of benefits that can enhance your fat-burning lifestyle. I personally use them daily as a strategy to heighten my mental performance and give my workouts an extra boost. For these purposes, I have also found it logical to combine exogenous ketones with other known health and performance boosting agents such as branched-chain amino acids and medicinal mushrooms.
If you are not on a vigorous exercise plan, I wouldn't go more than about a scoop a day (if you are a 30min/day, low carb person like me) because some of the research available says that if you get into ketosis using diet only and supplement with extra ketones, you may experience a slower rate of weight loss since you are getting your ketones from a supplement rather than the body transforming fat to ketones. As I progress, I will probably move up to 2 scoops per day.
Studies show that exercising depletes both liver and muscle glycogen faster than fasting [4]. For example, swimming for an hour and a half depletes the same amount of glycogen as a 24-hour fast. However, it's a good idea to eat a tiny amount of carbs and protein before and after a workout to prevent muscle damage. Your body can break down proteins in your muscles if glycogen stores get depleted during workouts.
How BHB turns into energy is a fairly simple process. As we’ve mentioned, beta hydroxybutryate eventually leads to energy production after you consume it or after your body breaks stored body fat down. It does this by going into the cell, entering the mitochondria (energy factories) at which stage it cleaves the carboxyl acid group and becomes acetoacetate (another “ketone body”). Acetoacetate turns into acetoacetyl-CoA, which then is cleaved to acetone (another “ketone body”) and acetyl-CoA. Acetyl-CoA is the whole reason we want BHB in the first place. This jumps into what is called the Kreb’s cycle (don’t you remember any of your biochemistry classes?) and is churned into ATP — the energy currency of your cells!

Caveat emptor: the following post doesn’t come close to answering most of these questions. I only document my experience with BHB salts (and a non-commercial version at that), but say little to nothing about my experience with BHB esters or AcAc esters. But it will provide you will some context and understanding about what exogenous ketones are, and what they might do for athletic performance. We’ll likely podcast about the questions and topics above and cover other aspects of exogenous ketones in more detail.

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