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.
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
Hello! I’m planning on taking a short vacation and will be having “kept friendly” drinks, mostly vodka and water with lemon and stevia. When should I take my exogenous ketones? That night before bed or early the next morning or after the 3 day vacation is completely over? I’m unsure how to manage this to have the best odds of staying in ketosis and get back to burning FAT. Also, I just purchased Instaketones from Julian Bakery, what are your thoughts on this brand? Thanks for what you do!
We carried out the testing across five different days, leaving at least two days between the different testing days so that my teammates had time to recover from the physical performance test each time. The reason we needed five days was that we included a placebo (an artificially flavored drink with no caffeine content) alongside the four brands we tested. Our teammates didn’t know that one of the supplements was a placebo. We also gave everyone a different supplement each time, to rule out any improvement in the tests being a result of people simply getting better at those tests over time.
Funding. This work supported by an Industrial DPhil Fellowship to BS from the Royal Commission for the Exhibition of 1851. JM was supported by the EPSRC Doctoral Training Centre and Prize Fellowship; Ref: EP/M508111/1. The funding sources were not involved in the design, conduct or analysis of this study. TΔS Ltd. provided the ketone ester, ΔG®, and NTT DOCOMO Inc. provided the acetone meter for the study.
There have been studies done on long term ketogenic diets. This 2004 paper inn Experimental & Clinical Cardiology titled ‘Long-term effects of a ketogenic diet in obese patients’ concluded that obese patients following a ketogenic diet for 24 ‘reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.’

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.
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.

Sure Leslie, the goal is to induce the burning of stored fat in your body. This process usually take a few days of strictly limiting carbohydrate intake. Supplementing with exogenous ketones is a way to shortcut the wait time, essentially “tricking” your body into ketosis. I imagine supplementing with too many could have negative effects on fat loss, but the research is not out supporting that claim yet.


That’s exactly what ketones do: inhibit lipolysis, the breakdown of body fat into triglycerides and free fatty acids for burning. In normal conditions where ketones are produced endogenously, this is expected and beneficial. If homemade ketones increased lipolysis, you’d end up with ketoacidosis. You’d make ketones which released more body fat which got turned into more ketones which released more body fat which became more ketones. And on and on. It simply wouldn’t stop.
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.

To be in ketosis, you need to get very specific about the macronutrient ratios hanging off your fork. This means eating 75% fats, 20% protein and 5% carbohydrates. It’ll see you getting 5-10% of your total calories from carbohydrates, which is roughly 25-30g of carbs per day, and diligently keeping this below the 50g threshold creates the ketosis that burns stored fat. Unlike the no-limit-protein option on the table when going low carb, eating more than 0.67-0.81g of protein per pound of bodyweight can hoof you out of ketosis because too much of it can be converted into glucose, blunting the benefits of the ketones. On the plus side, you will have a high fat intake, making your energy levels more balanced so you can train at higher intensities.
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).
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.
You may find a tiny amount here and there is ok (i.e., 2g of sugar with a meal full of fat may be ok).  But if you are starting out I would recommend cutting all sugar from your diet, and most importantly avoiding any sugar consumption on an empty stomach. For best results track your ketone levels before and after meals to see the impact the food has on your ketone levels.
If the claims about the benefits of exogenous ketones are accurate and true, then it’s fantastic news for people who are looking to enhance their keto lifestyle and who have the money to spend. But two of our core values are trustworthiness and goodness, and it is important to us to test assumptions made by marketing claims and help make sure that people are getting what they are told they are getting when they spend money on a product.
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.

Exogenous ketones cause the body to rely less on fat as fuel (see Fig 3). Fat takes longer to metabolise for energy than muscle glycogen. This is why fatty acids are not the preferred fuel under heavy exercise. This could be useful for keto-adapted athletes performing high-intensity cardiovascular or strength training.12 This is particularly useful for the Keto-adapted athlete who wants to undergo high-intensity cardiovascular or strength training.
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.
Our bodies are produce three types of ketone bodies for fuel: beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. Each is used by the body differently. Acetone is the least abundant, produced in much smaller amounts, and is usually exhaled through the lungs rather than being used as fuel.3 Acetoacetate is part of the metabolic pathway whereby humans make and use ketones, but it tends to be found in the blood at lower levels than BHB.
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?
In Summary, I think it’s important to do your own research and draw your own conclusion about the long term risks of ketosis. For some people, a ketogenic diet may be a necessity given their health situation. For those of us who do not suffer from such health conditions I would present the question ‘why do you want to follow a strict ketogenic diet for an extended period’, and then follow this up with ‘are the potential risks and sacrifices worth the benefits?’
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)
If you noticed that you're not getting into ketosis quick enough, chances are you're not eating enough fat. Eating plenty of healthy fat is essential in inducing ketosis. One reason why this is so is that your body makes ketones from fat. The other reason being that fat is highly satiating, so your body won't slow down or start breaking down muscle for fuel.

If you've tried this type of diet before, or if you've done some research about it beforehand, then you should know that these ten tricks are necessary to get into a ketogenic state quickly, but you will be surprised at the number of people who actually jump on the ketogenic bandwagon without knowing any of the basics first. Remember: A good working knowledge coupled with an effective meal plan can go a long way.
Usually, you’ll find exogenous ketones in the form of powdered ketone salts. Less common are ketone esters, which are the purest form of ketones. Griffin says they work quickly (in 10 to 15 minutes, as opposed to an hour for the salts) and effectively, but they’re more expensive, have a more-revolting taste, and are harder to find (HVMN is one U.S. company that sells them). People also use medium-chain triglyceride (MCT) oil — or partially manmade fats — to put the body into a state of ketosis.
An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017), in three extremely ill pediatric patients (Plecko et al., 2002; Van Hove et al., 2003; Valayannopoulos et al., 2011) and in cyclists (O'Malley et al., 2017; Rodger et al., 2017). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis. Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, d-βHB, and l-βHB, despite the metabolism of l-βHB being poorly understood (Webber and Edmond, 1977; Scofield et al., 1982; Lincoln et al., 1987; Desrochers et al., 1992). The pharmacokinetics and pharmacodynamics of KS ingestion in healthy humans at rest have not been reported.

Ketones are produced by the body as a indicator of the body starting to use fat for fuel. Your body then uses those ketones as brain fuel (mostly) , but if you were to have a carb meal it would kick your body out of ketosis (fat burning state) because the carbs are a more easily usable source of energy. So why would you want to add a outside source of energy such as ketones not naturally produced by the body its self? It would kick you out of the fat burning state just like the carbohydrate meal because your body rather spare it’s own energy source as much as possible and also since the outside source ketones are not naturally produce by the body your body does not go into fat burning state because it doesn’t have to go through the natural process to produce its own ketones meaning the body is in its fat burning state since ketones are a by product of fat being used as fuel. Your body has to go through the natural process by itself. Outside ketones are treated as a alternative fuel source so your body has no reason to use fat as its fuel source. Just like carbs. Don’t fall for the scam do your homework it’s science backed up by facts. https://www.t-nation.com/diet-fat-loss/avoid-this-ketogenic-rip-off

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.
So by taking in the perfect keto base, which are the exogenous ketones (BHB). This will easily put my body into ketosis rather than having to do the ketosis diet? I cant make up my mind on whether to buy the ketone powder and/or the MCT oil powder. What is the benefit of the MCT oil powder? When i read about it on the perfectketo website, it sounds like it does the same job as the perfect keto base. I’m also curious about the bone broths others sell for ketose related stuff. Is it very benedficial even when it has about 600mg of sodium in it?
In terms of epigenetic signaling, initial studies of the effects of BOHB on class-1 histone deacetylase activity against oxidative stress (Schimazu 2013), NLRP3 inflammasome suppression (Youm 2015), mouse longevity (Roberts 2017), and other epigenetic regulatory effects suggest that levels as low as 1 mM have potent effects. Furthermore, the association between very mild ketonemia and reduced coronary mortality with SGLT2 inhibitor use in patients with type 2 diabetes (Ferranini 2016) suggests that there might be clinical benefits with chronic BOHB levels as low as 0.3 mM (Gormsen 2017. Vetter 2017).
Geek note: Technically speaking, beta hydroxybutyrate is NOT a legitimate ketone body. Ketone bodies, or ketones are technically molecules with carbonyl carbons which are bonded to two additional carbon atoms. One carbon has four available bonds. When that carbon is double bonded to oxygen and also has two single bonds to carbon, we have a ketone body. If you have a carbon atom that is double bonded to an oxygen (carbonyl group), which is also bound to an -OH group instead of two different carbon atoms, that would be a carboxylic acid, but that really doesn’t matter in this case. For all intents and purposes of the ketogenic diet, betahydroxybutyrate should be considered one of the three ketone bodies and a “ketone” nonetheless. Your body uses BHB pimarily for energy in the state of ketosis, so it’s a ketone, okay?
But some people chose to use supplements to benefit from ketosis (Therapeutic Ketosis), and finally there is the MCT Ketogenic Diet – which in a form of nutritional ketosis (ULC, limited protein, high fat) with a twist – about 30-60% of the fat intake in the diet comes from MCT (Medium Chain Triglyceride) fats. Sources of MCT fats include Pure MCT Oil, Coconut oil and coconut products. The MCT Ketogenic Diet is often used with epilepsy suffers, as the high levels MCT oil create a higher level of ketones in the blood – which helps prevent seizures.

This research is a good reminder to discuss with your doctor before taking any supplements. Given the widespread use of calcium supplements, more research is required before any final conclusions can be drawn. Several ketone companies have tried to avoid the large sodium loads but instead relied on a bump in the calcium content from the BHB ketone salts, seemingly without consideration for the aforementioned results. Calcium BHB will likely absorb slower compared to sodium BHB due to digestion and absorption kinetics.  For those looking to optimize brain uptake of ketones, this probably isn’t the best strategy (as uptake is directly proportional to the levels in the blood).   Be cautious of supplements running from the sodium and chasing the calcium BHB instead, and make sure you factor that into your overall daily needs.


It's also important to note that you probably should follow a low carb diet or ketosis diet when using this product. Your brain prefers glucose as fuel because it's easier for the body to metabolize from food, so if you are eating a standard American diet of 100g+ carbs per day, or excessive protein, this won't help you lose weight, even with exercise because you'll have more than enough glucose to power your brain. Carbohydrate restriction, moderate protein, and lots of good healthy fat is what puts your body into ketosis.
But some people chose to use supplements to benefit from ketosis (Therapeutic Ketosis), and finally there is the MCT Ketogenic Diet – which in a form of nutritional ketosis (ULC, limited protein, high fat) with a twist – about 30-60% of the fat intake in the diet comes from MCT (Medium Chain Triglyceride) fats. Sources of MCT fats include Pure MCT Oil, Coconut oil and coconut products. The MCT Ketogenic Diet is often used with epilepsy suffers, as the high levels MCT oil create a higher level of ketones in the blood – which helps prevent seizures.

77. Volek JS, Sharman MJ, Gomez AL, Scheett TP, Kraemer WJ. An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr. 2003;133(9):2756–61. [PubMed]


This was a big surprise. We were at the very least expecting that drinking a ketone supplement would cause blood ketones to rise, but an average increase of 0.33 mmol/L is very small. The supplement associated with the highest average increase in blood ketones was Prüvit’s Keto-OS Max, but it was only an increase of 0.6 mmol/L. Brianna Stubbs, the ketone researcher I consulted with, agrees that an increase of below 2.0-3.0 mmol/L is unlikely to be of much use.
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.
Ketōnd is an intelligently designed formula containing an industry leading 13,900mg blend of high-powered goBHB™ all packed into a 100% transparent, proprietary blend free formula. Ketōnd is widely known as the most ‘potent’ exogenous ketone supplement available that has been formulated for anyone looking to manage their weight, maximize cognition, or simply feel more energetic in a low carbohydrate environment.
BHB Salts and exogenous ketone supplements are literally changing the supplement industry. These products are pretty new and a little more expensive than other supplements. But I’d rather pay for something that works then spend tons of money chasing products that claim to work. One of the most popular ketone supplements is Ketōnd. You can check out our review here.
Firstly, in a randomized four-arm cross-over study, blood βHB concentrations were compared following ingestion of equal amounts of βHB as a KE or a KS at two doses by healthy volunteers at rest (Study 1; n = 15). Secondly, in a randomized five-arm cross-over study, inter- and intra-participant repeatability of ketosis was examined following ingestion of identical KE drinks, twice whilst fed and twice whilst fasted. As a control, participants also consumed one isocaloric (1.9 kCal.kg−1) dextrose drink (Study 2; n = 16). Finally, blood d-βHB was measured after equal amounts of KE were given as three drinks (n = 12) or a constant nasogastric (NG) infusion (n = 4) (Study 3; total n = 14) over 9 h.
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.
Firstly, in a randomized four-arm cross-over study, blood βHB concentrations were compared following ingestion of equal amounts of βHB as a KE or a KS at two doses by healthy volunteers at rest (Study 1; n = 15). Secondly, in a randomized five-arm cross-over study, inter- and intra-participant repeatability of ketosis was examined following ingestion of identical KE drinks, twice whilst fed and twice whilst fasted. As a control, participants also consumed one isocaloric (1.9 kCal.kg−1) dextrose drink (Study 2; n = 16). Finally, blood d-βHB was measured after equal amounts of KE were given as three drinks (n = 12) or a constant nasogastric (NG) infusion (n = 4) (Study 3; total n = 14) over 9 h.

It comes in a small bottle that usually contains 50-100 strips depending on the type you choose. It’s very thin, and on one end there’s a small square of paper (this is the end you dip in the urine). If there are ketones in your urine, the little paper will change color. The darker it is (light pink up to a purple color) the more it is in your urine. On the bottle, there’s a picture you compare the color of the paper with that can be a very good indication of your current ketone state. 

The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.


As for MCT oil (and oil powders), powder formulations tend to cause less digestive distress (e.g. probiotics), but some folks object to the additional ingredients like sunflower lecithin or soluble corn fiber). Even if you’d like to eventually settle on an oil, I’d recommend starting with a powder to see how you respond and to give your body the chance to adapt over time.
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
Personally, I do this on Friday night to Saturday night, so if something happens and my hunger hasn't crashed by Sunday morning, I have another day that I can go zero carb to keep the momentum going. While the body will trigger ketosis as soon as you run out of glycogen, hunger is attached to your triglyceride and insulin levels, which might take an extra day to normalize.

If you have already mastered the Very Low Carbohydrate (VLC) or ketogenic way of eating, and/or are eating at a caloric deficit, exercising or fasting you are naturally creating the optimal conditions for your body to produce ketones and put your body into nutritional ketosis. By strict adherence to a well-formulated ketogenic diet (complete with higher levels of mineral salts) you should be able to produce all the ketones you need naturally (endogenously). If you are new or inexperienced in ketogenic eating however; or if you or a family member struggles to adhere to a ketogenic diet, then supplementation with exogenous ketones may be very beneficial. Not only will ketone supplements help to mitigate hunger and carb cravings, but they will also help you stave off carb flu symptoms (see below), giving you the best possible chance of long-term success.


Great question. We can’t see any reason this can’t be a part of a successful weight loss program on the ketogenic diet. In the morning with coffee is a very popular way to raise ketone levels in the morning. See if you are on pace with your goals and perhaps try a week with a different breakfast to see what feels best. Also – new article might be helpful here too: https://perfectketo.com/exogenous-ketones-for-weight-loss/ Good luck! 🙂
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).

d-βHB was measured immediately on whole blood using a handheld monitor and enzyme-based reagent strips (Precision Xtra, Abbott Diabetes Care, UK). Samples were stored on ice, centrifuged and duplicate plasma aliquots stored at −80°C. All urine passed during the visit was collected, the total volume recorded, and 1 ml aliquots taken, frozen and retained for analysis.


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.

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