Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
Emerging evidence supports the therapeutic potential of the ketogenic diet (KD) for a variety of disease states, leading investigators to research methods of harnessing the benefits of nutritional ketosis without the dietary restrictions. The KD has been used as an effective non-pharmacological therapy for pediatric intractable seizures since the 1920s [1–3]. In addition to epilepsy, the ketogenic diet has elicited significant therapeutic effects for weight loss and type-2 diabetes (T2D) . Several studies have shown significant weight loss on a high fat, low carbohydrate diet without significant elevations of serum cholesterol [5–12]. Another study demonstrated the safety and benefits of long-term application of the KD in T2D patients. Patients exhibited significant weight loss, reduction of blood glucose, and improvement of lipid markers after eating a well-formulated KD for 56 weeks . Recently, researchers have begun to investigate the use of the KD as a treatment for acne, polycystic ovary syndrome (PCOS), cancer, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI) and Alzheimer’s disease (AD) with promising preliminary results [14–26].
It was like getting the benefits of a five-day fast in just 15 minutes! As my body and brain began sucking up the ketones, I felt a rush of energy and my mind became very sharp and focused in ways beyond what I attain doing an extended fast. But in this case it was the 40g of ketones I had just consumed. Even at the two-hour mark, when I took my last reading, I was still in deep ketosis.
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 . Ketone bodies have been shown to increase the hydraulic efficiency of the heart by 28 %, simultaneously decreasing oxygen consumption while increasing ATP production . Thus, elevated ketone bodies increase metabolic efficiency and as a consequence, reduce superoxide production and increase reduced glutathione . Sullivan et al. demonstrated that mice fed a KD for 10–12 days showed increased hippocampal uncoupling proteins, indicative of decreased mitochondrial-produced ROS . 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 . 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.
When the results for the supplement and the placebo were within 0.2 (either % or mmol/L) of each other, we classed the supplement as neither “better” nor “worse” than the placebo. We gave a “winning brand” sticker to the brand that scored highest against the placebo for each marker, but not for physical performance, since none of the supplements performed better than the placebo for that marker.
If you’ve done any reading about ketosis, you no doubt read at some point that ketosis is a “natural” state. You may have read on a bit more and learned what is meant by that statement or you may have simply skipped ahead to the keto success stories and decided to give it a try. But we’d like to direct your attention back to that little tidbit of information about keto being “natural” for a moment.
It might sound absolutely crazy to go that long without food. Especially when you consider traditional diets that recommend eating 3-5 small meals each day, starting with breakfast – the “most important” meal of the day. But if you think back to hunter gatherer times, human beings didn’t always have food accessible to us. Farming and agriculture hadn’t existed so our first meal each day would vary quite vastly. If you think about the word itself, ‘breakfast’ means to break-fast. We didn’t have a set time where we would consume our first meal – it was dependent on accessibility. So if you’re wondering how you’re going to survive without going for food for 16 hours, the answer is straight forward – you can! Let’s simplify this and break down what this may potentially look like.
Our mission at Ketologie is to help educate and assist people in transitioning to a ketogenic way of eating for life. Primarily, we support people achieving this via adopting a VLCHF or ketogenic way of eating. Exogenous ketones can however play a useful role in transitioning to and maintaining a ketogenic lifestyle, and so we have exhaustively researched and developed a unique, “next level” ketone supplement that focuses specifically on optimizing health via the gut-brain axis.
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.
I stumbled onto this trend before it even blew up, I have read just about every peer-review journal of the topic, I have trialed as well as tested different methods and keto products (exogenous ketones, MCT oils, pills, etc), and lastly, I have reported and analyzed my performance to share with you all. It hasn't been an easy task, but I have also seen the fruits of the labor, and the fruit is sweet.
Blood, breath, and urine ketone kinetics following mole-matched ketone ester (KE) and ketone salt (KS) drinks, at two amounts, in 15 subjects at rest. Values are means ± SEM. (A) Blood d-βHB. (B) Tmax of blood d-βHB. (C) AUC of blood d-βHB. (D) Isotopic abundance (%) of d- and l-chiral centers in pure liquid KE and KS. (E) Blood d-βHB and l-βHB concentrations in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (F) d-βHB and l-βHB concentrations in urine samples from subjects (n = 10) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (G) Blood d- and l-βHB after 4, 8, and 24 h in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (H) Breath acetone over 24 h in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KE and KS drinks (ppm = parts per million). (I) Urine d-βHB excreted over 4 h after KE and KS drinks (n = 15). (J) Urine pH 4 h after drink, dotted line indicates baseline. †p < 0.05 KE vs. equivalent amount of KS, *p < 0.05 difference between 1.6 vs. 3.2 mmol.kg−1 of βHB, §p < 0.05 difference between amounts of d- and l-βHB, p < 0.05 difference between baseline and post-drink level.
Although most of the research has been done utilizing ketone esters, ketone salt supplementation has the potential to provide additional benefits through the extra electrolytes/nutrients that are required to make the ketones. While ketone esters are expensive due to the manufacturing process involved in making them, ketone salts might be a more convenient option for both inducing a state of ketosis and elevating blood ketone levels for various reasons we will discuss in another article.
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.
Those of you who have tried this form of weight loss before are probably more than aware of how hard it can be to first get your body to adapt to such a dramatic change in your daily intake of food, let alone without the help of a single exogenous ketone supplement. And the situation isn’t made any easier if you use a poor quality ketosis supplement because the wrong ketone product may actually do you more harm than good.
Increased levels of BHB in the body were found to be associated with greater cognitive performance through better performance in memory recall tests12 on a study of 20 subjects with Alzheimer’s disease or demonstration of a mild cognitive deficit. Similarly, BHB ketone esters helped to reverse symptoms of Alzheimer's Disease in one clinical case study.13 More research in humans is needed, but the various hypotheses are backed up by strong animal data.
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