Despite the recent growth of the ketone salt market, there is very little published work analyzing the effects of these products on any biomarkers or performance measurements in humans. Several studies have been carried out in rats,6,7 with blood BHB levels being relatively low (<0.5 mM) post-consumption of salt drinks. In humans, ketone salts provided peak D-BHB levels of 1 mM, whereas the same amount of BHB in a ketone ester (BD-BHB) raised blood BHB to 2.8 mM.5
Considering both the broad therapeutic potential and limitations of the KD, an oral exogenous ketone supplement capable of inducing sustained therapeutic ketosis without the need for dietary restriction would serve as a practical alternative. Several natural and synthetic ketone supplements capable of inducing nutritional ketosis have been identified. Desrochers et al. elevated ketone bodies in the blood of pigs (>0.5 mM) using exogenous ketone supplements: (R, S)-1,3 butanediol and (R, S)-1,3 butanediol-acetoacetate monoesters and diester . In 2012, Clarke et al. demonstrated the safety and efficacy of chronic oral administration of a ketone monoester of R-βHB in rats and humans [49, 50]. Subjects maintained elevated blood ketones without dietary restriction and experienced little to no adverse side effects, demonstrating the potential to circumvent the restrictive diet typically needed to achieve therapeutic ketosis. We hypothesized that exogenous ketone supplements could produce sustained hyperketonemia (>0.5 mM) without dietary restriction and without negatively influencing metabolic biomarkers, such as blood glucose, total cholesterol, HDL, LDL, and triglycerides. Thus, we measured these biomarkers during a 28-day administration of the following ketone supplements in rats: naturally-derived ketogenic supplements included medium chain triglyceride oil (MCT), sodium/potassium -βHB mineral salt (BMS), and sodium/potassium -βHB mineral salt + medium chain triglyceride oil 1:1 mixture (BMS + MCT) and synthetically produced ketogenic supplements included 1, 3-butanediol (BD), 1, 3-butanediol acetoacetate diester/ ketone ester (KE).
If you are trying to lose weight, following a ketogenic diet can help you burn fat fast. However, trying to get into ketosis can be a frustrating experience. Am I eating too many carbs, not enough fat, too much protein? Getting into ketosis usually takes 3 to 5 days at least, and can take people up to two weeks. Recently I have discovered a simple and easy way to get into ketosis very quickly. I went from eating lots of carbs one night, to in ketosis 24 hours later.
Also known as the carb flu, the keto flu is commonly experienced by people who are transitioning to a Ketogenic diet. “Keto flu” is not actually flu but mimics the experience of flu with very similar symptoms. It can happen when someone who has become accustomed to relying primarily on carbohydrates as fuel removes them from their diet. Whilst this is a necessary step towards adjusting from being a sugar-burner to a fat-burner, the sudden change can trigger some unpleasant symptoms, much like withdrawing from an addictive substance. Keto flu symptoms can include drowsiness, nausea, dizziness, achy muscles, mental fogginess and an irritable mood. The good news though, is that most of these experiences relate to dehydration and electrolyte depletion, and so are easily prevented or managed. Simply adding a ¼ - ½ teaspoon of a high quality sea salt or sodium/potassium powder to a glass of water works wonders; however you may still require a separate magnesium supplement; particularly if you are prone to muscle cramps or restless legs. Another popular way to manage your electrolytes is via a good quality bone broth powder. Finally, since BHB’s are normally delivered via a mineral salt base*, keto flu symptoms are easily prevented or reduced by using an exogenous ketone supplement powder.
For the ketone esters, on the other hand, repeated doses of 20-30 grams in any one day may be possible. Thus these products may be able to maintain a modest level of ketonemia without dietary carbohydrate restriction. Thus some of the cardiac and brain fueling benefits may follow, not to mention the epigenetic effects limiting oxidative stress and inflammation. But given the recent observation that administered ketone esters markedly reduce circulating free fatty acids (Myette-Cote 2018) — possibly due to an insulin-tropic effect or direct suppression of lipolysis (Taggart 2005) — their sustained use in people with underlying insulin resistance may compromise their long-term benefits by promoting weight gain unless combined with carbohydrate restriction.
Neuroprotection: As humans age, the brain becomes more susceptible to neurodegeneration and subsequent conditions such as Alzheimer’s and Parkinson’s disease. Exogenous ketone supplementation appears to ameliorate the typical decline in cognitive function that comes with aging. The likely mechanism for this neuroprotective property is that ketone bodies reduce the inflammation and hyperexcitability that is normally exhibited as glucose metabolism declines in the brain.18, 19
I am a little confused. I can see how EK’s can help up the state of ketosis, but as far is weight loss is concerned, aren’t the ketones you produce naturally created by the breaking down of your own fat? If I supplement with exogenous ketones, will that slow the natural creation of ketones? Especially if I am eating a higher amount of carbs. Would exogenous ketones speed fat loss, or slow it?
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
Concentrations of plasma non-esterified fatty acids, triacylglycerol, glucose, and insulin following equimolar ketone ester and ketone salt drinks, at two amounts, in subjects (n = 15) at rest. Values are means ± SEM. (A) Plasma FFA. (B) Plasma TG. (C) Plasma glucose. (D) Plasma insulin at baseline and after 30 and 60 min. EH, ketone ester high; EL, ketone ester low; SH, ketone salt high; SL, ketone salt low. *p < 0.05 difference from baseline value.
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.
“Imagining that everyone is going to go on a ketogenic diet is very unlikely. I’ve done it myself, and it is hard as a diet to sustain for a long period of time,” said Verdin. “The interest for us in BHB is [if] can we recapitulate all the beneficial effects that we are seeing from the ketogenic diet simply by administering BHB as a food or as a drug, whatever you want to call it.”
Relationship between blood ketone and glucose levels: a BMS + MCT (5 g/kg) supplemented rats demonstrated a significant inverse relationship between elevated blood ketone levels and decreased blood ketone levels (r2 = 0.4314, p = 0.0203). b At week 4, BMS + MCT (10 g/kg) and MCT (10 g/kg) showed a significant correlation between blood ketone levels and blood glucose levels (r2 = 0.8619, p < 0.0001; r2 = 0.6365, p = 0.0057). Linear regression analysis, results considered significant if p < 0.05
Another important difference between endogenous and exogenous BOHB is that most synthetic BOHB used in dietary supplements is a mixture of the two ‘D’ and ‘L’ isomers, whereas endogenously produced BOHB consists of just the D-isomer. Metabolically, the two isomers are very different, and current published information indicates that most of the energy and signaling benefits of BOHB derive from the D-form. This is potentially problematic because the L-isomers are not metabolized via the same chemical pathways as the D-forms (Lincoln 1987, Stubbs 2017), and it remains unclear whether humans can convert the L-form to the D-form.
More tolerable than MCT oil: MCT oil has been known to cause gastrointestinal distress in users, especially when taken in higher amounts. Exogenous ketones in the form of ketone salts, in comparison, are well-tolerated. Thus they enable one to avoid adverse GI events while providing the body with similar types of benefits. Figure 2 shows Ketone esters can be effective at reducing appetite. A combination of MCT oil and exogenous ketones may aid weight loss and allow a lower loading of ketone supplements, without the GI distress seen with MCT oil.
How did I do this? Simple, I went into a full fast and exercised. What prevents you from entering ketosis is all the glycogen stored in your liver and muscles. Your body can use this glycogen instead of ketones to fuel your brain, so until you deplete your stores of glycogen, you won’t be able to enter ketosis. By eating nothing, you are going to tap into the glycogen to fuel your brain because you are eating 0 grams of carbs and will also be using that glycogen to walk around all day.
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 .
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.
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.
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.
Not only is Ketōnd considered one of the best on ketone supplements the market it also currently holds favorable ratings, reaching numbers as high as 98 percent in customer reviews. They absolutely love this product and you will too if you give it a try. You will get some incredible results. Whether you are a busy professionals, athlete, on-the-go moms or dads, or college students you too will love this product.
And zero-carb, followed by fasting for two meals, and then followed up by a second zero-carb meal is almost always all you need to get into ketosis fast. By Sunday or Monday morning, after a second night of no carbs, you'll be in a deep enough ketosis that hunger will crash and your energy will surge to help you transition into your low-carb diet of choice.
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.
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…
But there have also been studies done showing that the Inuit Eskimo’s do not actually reach a state of ketosis. This is due to numerous factors. One being that the diet the eskimo’s eat ‘would not be expected to cause ketosis, because the calculated anti-ketogenic effect of the large protein ingestion was somewhat more than enough to offset the ketogenic effect of fat plus protein.”
The year before last I somehow full on Rocked at the keto diet lost 100lb, and was taking adderall. I am transitioning back into it again also back on the adderall, but i seem to have no energy and last time my doc did my blood work i was only 16% hydrated. Obviously it’s a huge problem for me, staying hydrated and trying to lift the fogginess. I am type 2 diabetic and my doctor is on board with me trying all to keep my sugars down YEAH!!! I have never tried any exogenous product. My body seems to not absorb much vitamins. Can anyone make a or any suggestion to me as to how to get this under control?
Even though endurance athletes can train in a carb depleted state, they will generally consume carbohydrates in the lead up to a race (the athlete is seeking to increase the ability to run off fats by training in a carb depleted state, then benefiting from both fats AND carbs come race day). Likewise, with the brain, even though the brain can function off ketones, does it mean it’s the best state for brain function?
Effects of ketone supplementation on blood glucose. a, b Blood glucose levels at times 0, 0.5, 1, 4, 8, and 12 h (for 10 dose) post intragastric gavage for ketone supplements tested. a Ketone supplements BMS + MCT and MCT significantly reduced blood glucose levels compared to controls for the duration of the 4-week study. BMS significantly lowered blood glucose only at 8 h/week 1 and 12 h/week 3 (b) KE, maintained at 5 g/kg, significantly reduced blood glucose compared to controls from week 1–4. BD did not significantly affect blood glucose levels at any time point during 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)
I I started off interested in this product because it was cheaper than another popular Keto drink that I have known people to loose weight on. I have been drinking this about 2 weeks every morning on my way to work and I have never gotten the shakes jitters or felt a crash. I have also noticed my clothes to fit more comfortably as well. I do feel somewhat better taking this product I don’t know if it’s a mental thing but I will definitely purchase more and keep drinking it to hopefully see more difference
I just read your comment and was wondering the same thing. I can see how exogenous ketones can be a great energy boost to people on the ketogenic diet, but I don’t see how they can speed fat loss. Keto OS claims you can eat higher carbs and still see the benefits of ketosis. I don’t see how that is possible. the whole point of weight loss through ketosis is the breaking down of your own fat to create energy. I don’t see how exogenous energy will increase natural fat breakdown. I wish I could get a straight answer to this from somebody.
Testing BHB levels in the blood is simple but can get pricey if you are doing it many times a day. The Precision Xtra blood glucose and ketone meter is a good buy at $28-$30. The expensive part is the ketone test strips here which can cost $4 each. If you are looking at testing yourself every day it is going to cost you $120 a month and the $30 meter. Here is a starter kit you can get on Amazon.
And zero-carb, followed by fasting for two meals, and then followed up by a second zero-carb meal is almost always all you need to get into ketosis fast. By Sunday or Monday morning, after a second night of no carbs, you’ll be in a deep enough ketosis that hunger will crash and your energy will surge to help you transition into your low-carb diet of choice.
Keto-adaption is a complex set of metabolic processes in which the body shifts from using primarily glucose for energy to using largely ketones and fat for energy. Achieving ketosis doesn’t mean the body is maximizing the use of these ketones; it takes longer than a few days for the body to get used to burning fat and ketones as its predominant fuels.
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.”
Beta-hydroxybutyrate (BHB) is a ketone body produced in the liver naturally under conditions when glucose isn’t very available. Other types of ketones produced via the restriction of dietary carbohydrates are acetoacetate and acetone. A VLCHF or ketogenic diet provides the optimal conditions for this process. Fasting, exercise and/or basic caloric restriction are all also methods for promoting ketogenesis (literally, the making of ketones).
 Shannon L. Kesl, corresponding author Angela M. Poff, Nathan P. Ward, Tina N. Fiorelli, Csilla Ari, Ashley J. Van Putten, Jacob W. Sherwood, Patrick Arnold, and Dominic P. D’Agostino (2016). Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutrition & Metabolism, 13(9)
We will go deep in the science behind this fascinating diet and then review some of the best exogenous ketone supplements out there in the market. Because without the knowledge and the right information about exogenous ketones that you can properly follow, you might never reach your goals and you may as well keep eating that mashed potato for dinner and club sandwich for lunch.
Ketone supplements contain exogenous ketones—synthetic ketones made in a lab. Most use a type of ketone called beta-hydroxybutyrate (BHB), which is the same as the ketones the body produces naturally. “We’re literally biohacking," says Amie Heverly, who began taking a ketone supplement called Prüvit last year and now works as a promoter selling Prüvit products. "You’re not adding a foreign substance to your body, because BHB is identical to what your body would naturally produce,” she explains.
We designed a test for each of the chosen benefit claims and enlisted the help of four of our Diet Doctor teammates to try out the supplements and go through the testing. They were Jonatan and Giorgos from the video team, Emőke from the recipe team and Erik from the IT team. We had a mix of people who were naturally in endogenous ketosis during testing, and people who were not.
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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