Uncontrolled diabetics may face some risks in using exogenous ketones. This is because when the body is unable to produce insulin (type I diabetics and extreme type II diabetics), it is unable to get sugar or glucose into the cells. Therefore, the body will start producing ketones. If these individuals do not use an insulin injection, they can overtime build up unsafe levels of ketones (6).
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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.
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.
An effective ketosis program requires that you control your appetite. Caffeine has been proven to be an excellent appetite suppressant. It can curb your appetite and reduce your cravings for food. If you are finding it hard to implement intermittent fasting, try to introduce coffee into the equation. If you are not into coffee drinks, try to take tea or use caffeine pills. Both of them contain caffeine, which can help you to adjust smoothly into fasting.
Also, it’s important to remember that just because something may be SAFE (and to reiterate, I’m not saying a long term ketogenic diet is safe), it doesn’t mean it’s good for you or beneficial. Running Marathons could be considered safe (especially if it’s on a closed race circuit), but does this mean it’s good for you? Or should you be out running marathons every day?
I don’t recommend that you go straight for a 1-2 day fast, but begin by restricting yourself to certain eating windows. Typically people restrict themselves to the hours of 5pm – 11pm. People often refer to their fasting windows by numbers: 19/5 or 21/3, for example, means 19 hours of fasting and 5 hours eating or 21 hours fasting and 3 hours eating, respectively.
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
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.
Improved cognition: Elevated plasma ketone concentrations divert the brain to utilize ketone bodies for synthesis of phospholipids, which drives growth and myelination. Normally, glucose would be the preferred substrate, which is much less efficient.14 BHB seems to act as a signal for neuronal pathways. These enhance synaptic plasticity, cognition and neuronal stress resistance. 15 In rat studies, ingestion of a ketone ester for 5 days improved their spatial learning and memory. 16.
That’s not all. Though Prüvit in particular has a legion of fans (the brand has nearly 35,000 Instagram followers and some 256,000 likes on Facebook) and a small team of affiliated medical experts, there’s no hard science on Prüvit or similar products. (Prevention reached out to several Prüvit experts and employees for interviews but did not receive a response.) The research page on the brand’s website does include links to legit scientific studies. But the studies are on the keto diet—not on Prüvit’s products. When it comes to research on the actual supplements, the brand’s website simply says “Human studies on finished products (underway) at various universities and research facilities.” In other words, there’s no scientific evidence available yet to show that they actually work.
Fortunately, you don’t need to be a dietary math savant to cash in on these rewards because the supplement eggheads took the liberty of creating exogenous ketones, which act as direct substitutes to the ones your body creates. Unlike other fat burners that give you the skits jitters, these are actually helping exercisers reach new personal bests while getting leaner, and are totally legal. Here’s what you need to know to get a slice of the action safely.
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.
Too much cortisol tells the liver that you are in physical danger and need a lot of energy fast. The brain doesn’t understand the difference between physical danger and emotional stress. When emotionally stressed, the brain thinks you’re in a life-and-death situation, so the liver comes to your rescue and gives you the glucose you need to fight off your attacker.
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.
Effects of ketone supplementation on organ weight: Data is represented as a percentage of organ weight to body weight. a, b, d, f Ketone supplements did not significantly affect the weight of the brain, lungs, kidneys or heart. c Liver weight was significantly increased as compared to body weight in response to administered MCT ketone supplement compared to control at the end of the study (day 29) (p < 0.001). e Rats supplemented with BMS + MCT, MCT, and BD had significantly smaller spleen percentage as compared to controls (p < 0.05, p < 0.001, p < 0.05). Two-Way ANOVA with Tukey’s post-hoc test; results considered significant if p < 0.05. Error bars represent mean (SD)
However, with the ketone esters, the effects are nearly immediate, and my entire body was humming throughout the entire day, but not in a jittery way. I was full of mental and physical energy that lasted without any sort of crash (it was a gradual taper). During my cognitive tests, things felt almost effortless as I played the various games. After my experiment was complete I continued writing code for several hours, then went to the gym to work out. I did forget to each lunch though, so there must be some suppressive effect on appetite.
I don’t think we even need a drumroll here… Based on my background research into ketone-supplement companies, the survey of Diet Doctor users and the experiment itself, we cannot recommend taking these supplements. I can personally think of many more beneficial ways to invest money in my health, such as buying grass-fed meat and organic vegetables, or even buying a bicycle and riding it outside in the sunshine.
The difference in peak blood d-βHB concentrations between matched amounts of βHB as ester or salts arose because the salt contained l-βHB, as the blood concentrations of d- plus l-βHB isoforms were similar for both compounds. It is unclear if kinetic parameters of KE and KS drinks would be similar if matched d-βHB were taken in the drinks. Unlike d-βHB, blood l-βHB remained elevated for at least 8 h following the drink, suggesting an overall lower rate of metabolism of l-βHB as urinary elimination of l-βHB was in proportion to plasma concentration. Despite similar concentrations of total βHB, breath acetone was ~50% lower following KS drinks compared to KE, suggesting fundamental differences in the metabolic fates of D- and L-βHB. These findings support both previous hypotheses (Veech and King, 2016) and experimental work in rats (Webber and Edmond, 1977), which suggested that the l-isoform was less readily oxidized than the d-isoform, and is processed via different pathways, perhaps in different cellular compartments. It seems that l-βHB is not a major oxidative fuel at rest, and may accumulate with repeated KS drinks. However, the putative signaling role of l-βHB in humans remains unclear. In rodent cardiomyocytes, l-βHB acts as a signal that modulates the metabolism of d-βHB and glucose, Tsai et al. (2006) although no differences in blood glucose were seen here. Furthermore, L-βHB can act as a cellular antioxidant, although to a lesser extent than D-βHB (Haces et al., 2008).
I’m often asked if it’s necessary to buy and use keto products like urine sticks. They’re small test strips that you dip in urine to see if your body is producing ketones (and therefore indicate if you’ve entered ketosis.) There's very little information on how to know that you are in ketosis other than using these ketones supplements because they are as accurate as can be in determining your current state. Outside of that, you can only guess if you are in it or not by your body's performance.
The way you make an exogenous BHB is by attaching it to some type of other compound (sodium, potassium, calcium, or magnesium) so that your body can process the molecule by cleaving the bond between the salt and the beta hydroxybutyrate. BHB + bound to a salt = BHB salts, which is what most people in the ketosis community call exogenous ketones. There are also things called esters, which are basically unbound BHB molecules. These are really disgusting and cause massive digestive issues, so I like to ignore them until we can produce them in a more appealing way.
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.
Slowly ramp up your ketone intake. Be patient! 🙂 For many of us, our bodies aren’t used to running on ketones, so you can expect an adjustment period. Try ¼ scoop first. Transitioning to ketosis removes water from our bodies, so getting lots of water will help with any dehydration and stomach issues. Ramp up from there, trying ½ scoop the second week or when you feel it’s appropriate, and then try a whole scoop 1-2 weeks in. You can use it for extra energy or to help get into ketosis if you aren’t there already. Most people use it 0-3 times per day.
The effects of ketone drinks on endogenous insulin secretion are unclear. Whilst the small increase in plasma insulin after KE and KS drinks may have been due to the small quantity of dextrose in the diluent, it has been proposed that ketones could potentiate or even stimulate insulin secretion. Isolated pancreatic islets secreted insulin when stimulated by ketones at glucose concentrations of >5 mM (Biden and Taylor, 1983), and small amounts of insulin are secreted in vivo following exposure to exogenous ketones in animals (Madison et al., 1964; Miles et al., 1981). In response to an intra-venous 10 mM glucose clamp, ketone ester drinks increased glucose uptake and plasma insulin (Holdsworth et al., 2017). The increases in insulin with ketone drinks taken whilst fasted were small compared to the increases seen when the ketone ester drink was consumed with a meal and with consumption of a dextrose drink. Furthermore, the lack of difference in peak plasma insulin between the two latter conditions indicates that nutritional ketosis did not inhibit or increase normal carbohydrate induced insulin production.
Beta-hydroxybutyrate (BHB): Nutrition strategies that rely on carbohydrates always leave us needing more food. On the other hand, the ketogenic diet relies on and taps into your body’s stored fat for longer, more stable energy with no bonking. Many keto-lovers adopt this lifestyle because they love the mental clarity, focus, and productivity that they experience while in ketosis. Whether you’re full-time keto or not, our Perfect Keto is designed to support ultimate mental performance.
The other option – which is the superior option – is the breakdown of fat into a fuel that can be used by the brain. This is a beautiful solution, because even the leanest individual will have weeks and weeks’ worth of energy stored as body fat. The body breaks down this fat in the liver and converts it into ketone bodies. The brain can then utilise these ketones as a fuel source – forgoing the need for stored glucose or constant consumption of carbohydrates. These ketones can also be used to make ATP.
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)
Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.
What is the reason for needing to keep our stress levels down? Well the body reacts to stress, whether physical or emotional, by dumping glycogen and potentially glucose in your bloodstream, thus elevating insulin levels. This in turn blocks our bodies from entering ketosis. To keep your mental and emotional stress to a minimum, it may be wise to meditate, sleep, relax, or do something that is fun and care-free.
Even Ben Greenfield Has Thyroid Problems While In Ketosis - “Ben describes one of the main side effects that he encountered being severe hypothyroidism… manifesting as severe sensitivity to cold, poor libido, and poor overall energy. The way they treated this was to eat a lot of liver, desiccated thyroid, and sweetbreads which seemed to fix things for him.”
The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat . The macronutrient ratio of the KD induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) in the blood. Acetone, generated by decarboxylation of AcAc, has been shown to have anticonvulsant properties [28–32]. Ketone bodies are naturally elevated to serve as alternative metabolic substrates for extra-hepatic tissues during the prolonged reduction of glucose availability, suppression of insulin, and depletion of liver glycogen, such as occurs during starvation, fasting, vigorous exercise, calorie restriction, or the KD. Although the KD has clear therapeutic potential, several factors limit the efficacy and utility of this metabolic therapy for widespread clinical use. Patient compliance to the KD can be low due to the severe dietary restriction - the diet being generally perceived as unpalatable - and intolerance to high-fat ingestion. Maintaining ketosis can be difficult as consumption of even a small quantity of carbohydrates or excess protein can rapidly inhibit ketogenesis [33, 34]. Furthermore, enhanced ketone body production and tissue utilization by the tissues can take several weeks (keto-adaptation), and patients may experience mild hypoglycemic symptoms during this transitional period .
Ketone Salts: While the body uses and makes BHB ketones salts naturally, in supplement form ketone salts are synthetically (lab) made compounds that combine sodium (and/or potassium, calcium, or magnesium) with BHB. The salt is used to raise the pH and make things less acidic. Currently, all ketone supplements on the market are made from ketone salts. While they raise ketone levels, most people will only experience mild nutritional ketosis (~0.6-1.0 mmol/L).
It is important to define what it means to be “in ketosis”. If being “in ketosis” means having ketones in your blood, then of course ketone supplements get you into ketosis. But that is different from being in an endogenous ketogenic, fat-burning state as a result of following a ketogenic diet. Getting this distinction right will go a long way towards stopping ketone salts companies from using misleading marketing about the issue. We need to reach a consensus about what being “in ketosis” means and then force companies to use that definition.
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.
We sampled each of the 3 flavors and also mixed in the available Ketōstax and this supplement tasted better than any other we had tried. Ketōnd costs $79.95 for 30 servings which is about $2.67 per serving – which is less than half the price of the leading competitor. Ketōnd’s label and ingredients are 100% transparent, so they disclose everything that is in the supplement – which is only ketones. What we really liked about Ketōnd is that it isn’t part of some Multi Level Marketing company so there are no obligations.
One common concern regarding the KD is its purported potential to increase the risk of atherosclerosis by elevating blood cholesterol and triglyceride levels [55, 56]. This topic remains controversial as some, but not all, studies have demonstrated that the KD elevates blood levels of cholesterol and triglycerides [57–62]. Kwitervich and colleagues demonstrated an increase in low-density lipoprotein (LDL) and a decrease in high-density lipoprotein (HDL) in epileptic children fed the classical KD for two years . In this study, total cholesterol increased by ~130 %, and stabilized at the elevated level over the 2-year period. A similar study demonstrated that the lipid profile returned to baseline in children who remained on the KD for six years . Children typically remain on the diet for approximately two years then return to a diet of common fat and carbohydrate ingestion . The implications of these findings are unclear, since the influence of cholesterol on cardiovascular health is controversial and macronutrient sources of the diet vary per study. In contrast to these studies, the majority of recent studies have suggested that the KD can actually lead to significant benefits in biomarkers of metabolic health, including blood lipid profiles [65–72]. In these studies, the KD positively altered blood lipids, decreasing total triglycerides and cholesterol while increasing the ratio of HDL to LDL [68–77]. Although, the KD is well-established in children, it has only recently been utilized as a strategy to control seizures in adults. In 2014, Schoeler and colleagues reported on the feasibility of the KD for adults, concluding that 39 % of individuals achieved > 50 % reduction in seizure frequency, similar to the results reported in pediatric studies. Patients experienced similar gastrointestinal adverse advents that have been previously described in pediatric patients, but they did not lead to discontinuation of the diet in any patient .
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.
Zenwise, you should consider offering this through an email subscriber list to gain **more** loyal (& repeat) customers by offering them better prices. We all know it's cheaper to find ways to keep customers than to go out and find new ones (about 5x cheaper in fact!), plus my guess is Amazon is getting 30% margin AT LEAST). If I saw that you offered a 25% discount when buying directly, I'd keep using the product.
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