Animal procedures were performed in accordance with the University of South Florida Institutional Animal Care and Use Committee (IACUC) guidelines (Protocol #0006R). Juvenile male Sprague–Dawley rats (275–325 g, Harlan Laboratories) were randomly assigned to one of six study groups: control (water, n = 11), BD (n = 11), KE (n = 11), MCT (n = 10), BMS (n = 11), or BMS + MCT (n = 12). Caloric density of standard rodent chow and dose of ketone supplements are listed in Table 1. On days 1–14, rats received a 5 g/kg body weight dose of their respective treatments via intragastric gavage. Dosage was increased to 10 g/kg body weight for the second half of the study (days 15–28) for all groups except BD and KE to prevent excessive hyperketonemia (ketoacidosis). Each daily dose of BMS would equal ~1000–1500 mg of βHB, depending on the weight of the animal. Intragastric gavage was performed at the same time daily, and animals had ad libitum access to standard rodent chow 2018 (Harlan Teklad) for the duration of the study. The macronutrient ratio the standard rodent chow was 62.2, 23.8 and 14 % of carbohydrates, protein and fat respectively.
Ketone Esters: Synthetically-made compounds that link an alcohol to a ketone body, which is metabolised in the liver to a ketone. Ketone esters are used primarily in research for testing their efficacy in elevating ketone body levels (below is a generic structure of a BHB ester). Yet, the first commercial Ketone ester drink will be available in 2018 by HVMN. Research esters are reportedly very unpleasant tasting which HVMN hopes to change.
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.
It’s not clear that the Weir coefficients used to estimate EE are relevant for someone in ketosis, let alone someone ingesting exogenous BHB. (The Weir formula states that EE is approximated by 3.94 * VO2 + 1.11 * VCO2, where VO2 and VCO2 are measured in L/min; 3.94 and 1.11 are the Weir coefficients, and they are derived by tabulating the stoichiometry of lipid synthesis and oxidation of fat and glucose and calculating the amount of oxygen consumed and carbon dioxide generated.) While this doesn’t impact the main observation—less oxygen was consumed with higher ketones—it does impact the estimation of EE and substrate use.
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.
After a minimal amount of internet "research," I decided to try my first exogenous ketones. I have used the ketogenic diet off and on for at 15 years and my body is pretty efficient at fat adapting. (Usually by the end of 2 strict days, I am in ketosis, but not without symptoms and intense cravings.) I can consistently fast from carbs for 20 - 24 hours and do this consistently. However, around hour 20, my mind begins to negotiate that intermittent fasting is advantageous too and that I can afford to have some carbs once a day. Hence the yo-yo effect.
Let’s take a look at some of the facts and misconceptions about three of the minerals used to make ketone mineral salts: sodium, calcium, and magnesium. Potassium is very hygroscopic, meaning that it absorbs water very easily. Therefore, it is only feasible that it can be utilized in liquid formulations. Thus, one should be cautious if companies say they have potassium BHB salt powder in their product. I’d be very surprised if that’s actually the case.
Ketone Bodies are then used by tissues as a source of energy3 through a pathway that leads to formation from β-hydroxybutyrate of two molecules of acetyl CoA, which are used finally in the Krebs cycle. It is interesting to note that the KBs are able to produce more energy compared with glucose because of the metabolic effects of ketosis—the high chemical potential of 3-β-hydroxybutyrate leads to an increase in the ΔG0 of ATP hydrolysis.3
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.
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.
And now, you can take ketone supplements (salts and esters), known as exogenous ketones, without actually restricting anything. According to those promoting this nasty-tasting supplement, that means you can have a brain and body fuelled by ketones, along with all of the supposed health benefits that come with running on fat. Well, don't fall for it.
Exogenous ketones supplements is also necessary if you’re wondering how to get into ketosis in 24 hours. Directly ingesting ketones via salts or esters will boost blood ketone levels in the system. These are generally made up of beta-hydroxybutyrate (BHB) which is processed by the body to metabolise into ketones for energy. Some benefits of taking such supplements include anti-inflammatory properties, cancer prevention, increased cognitive function, weight-loss, and athletic performance enhancement.
There is also evidence that individuals who adhere to a low-carbohydrate or ketogenic diet may require higher sodium intakes. Due to their low carbohydrate contents, these diets reduce insulin levels. Since one of insulin’s roles is to decrease the excretion of sodium in the urine, low-carbohydrate and ketogenic dieters excrete more sodium than normal, and are encouraged to salt their meals to increase their sodium intake.
KE was synthesized as previously described . BMS is a novel agent (sodium/potassium- βHB mineral salt) supplied as a 50 % solution containing approximately 375 mg/g of pure βHB and 125 mg/g of sodium/potassium. Both KE and BMS were developed and synthesized in collaboration with Savind Inc. Pharmaceutical grade MCT oil (~65 % caprylic triglyceride; 45 % capric triglyceride) was purchased from Now Foods (Bloomingdale, IL). BMS was formulated in a 1:1 ratio with MCT at the University of South Florida (USF), yielding a final mixture of 25 % water, 25 % pure βHB mineral salt and 50 % MCT. BD was purchased from Sigma-Aldrich (Prod # B84785, Milwaukee, WI).
Halitosis (bad breath) – If you’re on a ketogenic diet you are probably aware that as the body starts to metabolize fat, ketones can cause poor breath. There is very little one can do about this, it’s just the nature of the beast. Unfortunately, this can also arise when using exogenous ketones, but it’s not as lasting as when on a ketogenic diet. Chewing gum or mints is about the best option if it becomes a noticeable issue. This maybe caused by over consumption of the ketone supplement, tailoring the quantity consumed may prevent excess BHB being converted to acetone, which is likely excreted by the lungs.
Effects of ketone supplementation on body weight: Rats administered ketone supplements gained less weight over the 4-week period; however, did not lose weight and maintained healthy range for age. KE supplemented rats gained significantly less weight during the entire 4-week study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls over weeks 2–4.MCT supplemented rats gained significantly less weight than controls over weeks 3–4, Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
I’m just getting back into an active lifestyle after being sedentary for a few years.. Rough start I must admit but I’m focused.. Objective is to lose 80lbs. I’ve previously had my body in ketosis when I was dieting and working out so I can attest to the benefits I’ve felt before.. Now that I see Exogenous Ketones are available, I’m wondering if it’s recommended to start taking them to help jumpstart my body into ketosis since that is the goal for burning fat…
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].
Some general side effects of your body producing beta hydroxybutyrate is essentially the lull in time it takes to switch from carbohydrate metabolism to fat metabolism, which can take 3-4 days. This can lead to mood swings, fatigue, and general low energy. If you want to skip that step, we recommend taking exogenous BHBs to switch your body over effortlessly.
Proper sleep is important for hormone function and repair of the body. Not getting enough sleep is tough on the adrenals and blood sugar regulation. Try to get at least seven hours of sleep per night. If you struggle with quality sleep, create an environment that is conducive for rest. This could be keeping your room cooler, turning off all electronic devices one to two hours before bedtime or using a sleep mask.
When you start this process, changes in your daily food and drink intake are designed to increase the amount of healthy fats being burned by your liver, which produces and releases more of these endogenous ketones into your blood stream. When breastfeeding, the female body naturally burns more fat to produce the endogenous ketones, which is an infants resource to the nutrients they need for their young minds. As an adult, a lot of us have substituted the goodness of this compound for more sugar fueled energy. However, I'm sure there are many of you that are wondering right now, "does keto work at all and if so how long does ketosis last?" After numerous tests and studies, it has been recognized that it indeed does work and has been proven to have long lasting effects, so you can rest easy and maybe throw away those weight loss pills that claim instant results but don’t seem to do much.
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).
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).
BHB easily crosses the blood-brain barrier resulting in easily accessible energy to the brain and muscle tissues, becoming a source of energy after entering the mitochondria, being converted to Acetyl-CoA, and then ATP through the Krebs cycle (the same process that glucose goes through to become ATP). This ultimately results in many direct benefits, including:
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