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.
Some think so because higher ketone levels imply increased fuel for the brain and heart (that prefer ketones), and increased protection against inflammation and oxidation. But are the health benefits coming from the ketones themselves, or are they coming from the state you have to put your body in to actually produce them? And if you're kicking yourself out of ketosis by ingesting ketones would you still get the same benefits?
It’s sometimes the case that a person has been attempting to transition to a state of ketosis, but in spite of their best efforts, they seem stuck in a kind of limbo where they’re eating hardly any carbs, but they don’t seem to be losing weight or experiencing the other benefits of the keto diet. But the science is the science, which means if you’re doing everything right you should be in ketosis. If you’re not, or you seem to be drifting in and out of a keto state, it’s not your body’s fault, it’s your diet.
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?
Should We Use Exogenous Ketones? Ketosis serves a purpose, and it’s probably why we’re able to survive on this planet. Being able to go without eating and use stored fats for energy is a survival tool and possibly far more as we’re now seeing with the keto diet. But it’s probably not a good idea to constantly take exogenous ketones and eat a high carb diet (high blood glucose levels). It’s not natural for the body to have high blood glucose and use ketones. This is a personal opinion, so
First, there’s something unnatural about having elevated levels of ketones and glucose together. It’s really hard to make that happen using traditional whole foods. The closest natural approximation you could get to it would be the traditional coconut-rich diets of the Kitava people in the South Pacific, where the medium chain triglycerides (MCT) in the coconut fat increased ketone production alongside the carbs in the fruit and tubers they ate. They had excellent metabolic health, but they weren’t anywhere close to a ketogenic diet. Coconut fat isn’t as ketogenic as purified MCT oil, let alone exogenous ketones.
At day 29 of the study, animals were euthanized and brain, lungs, liver, kidneys, spleen and heart were harvested and weighed. Organ weights were normalized to body weight. Ketone supplementation did not significantly change brain, lung, kidney, or heart weights compared to controls (Fig. 5a, b, d, f). MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05) (Fig. 5c). Ketone supplements BMS + MCT, MCT and BD caused a significant reduction in spleen size (BMS + MCT p < 0.05, MCT p < 0.001, BD p < 0.05) (Fig. 5e). Rats administered KE gained significantly less weight over the entire study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls during weeks 2 – 4, and MCT animals gained less weight than controls at weeks 3 – 4 (Fig. 6). Increased gastric motility (increased bowel evacuation and changes to fecal consistency) was visually observed in rats supplemented with 10 g/kg MCT, most notably at the 8 and 12-h time points. All animals remained in healthy weight range for their age even though the rate of weight gain changed with ketone supplementation [53–54]. Food intake was not measured in this study. However, there was not a significant change in basal blood glucose or basal blood ketone levels over the 4 week study in any of the rats supplemented with ketones (Fig. 7).
Will taking exogenous slow down my fat loss? Since now before digging into my body for energy/ketones, I will first use up the exogenous ketones I ingest. Also do exogenous ketones somehow help get even more keto adapted, keeping in mind I have been on a strict keto diet without a problem and don’t mind it at all. Outside of performance improvements, do you think exogenous ketones is for someone like me who is primarily looking for fat loss.
The many roles of magnesium include helping us maintain normal nerve and muscle function, as well as heart rate, supporting a healthy immune system, regulating blood glucose levels, and making energy production and protein synthesis possible. Magnesium is also involved in both aerobic and anaerobic energy production. ATP synthesis (the body’s energy source) depends on enzymes that are activated by magnesium.
The fate of excess ketones: In the event someone has an excessive amount of ketones in the blood, the body (specifically the kidneys) will work as quickly as possible to filter out ketones via urine rather than converting them to adipose tissue.9 This is not to say that you can’t gain fat if you consume an exorbitant amount of exogenous ketones, but that they are less prone to be converted to fat than other nutrients.
For the first part of my experiment, I would simply record my blood ketone and glucose levels over a period of two hours after taking the ketone esters. While I am already fairly keto-adapted and can attain nutritional ketosis fairly easily (> 0.5 mmol/L), it wasn’t until the end of my Five-day Fasting Mimicking Diet that I was even close to reaching therapeutic ketosis levels (>5.0 mmol/L).
There is one viable explanation for consuming ketones. If you're in a calorie or carb-restricted state, then maybe during a workout it would make sense. But even then, that really only applies to endurance activities, since it has more to do with enhancing aerobic performance (where oxygen is required), than it does with enhancing high-intensity efforts (where it's not).
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.
If you truly want to optimize health and performance, magnesium should not be neglected. There is still more research to be done on its potential. Good sources of magnesium include whole grains, nuts, seeds, legumes, green leafy vegetables, and supplements. However, be careful about taking too much magnesium at one time, or else you might end up running to the bathroom in a hurry.
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).
The ketone supplements were associated with a 5.4% decrease in physical performance while the artificially-sweetened, non-caffeinated beverage I used as a placebo was associated with a 20.3% increase: a big difference in favour of the placebo. Before you go rushing out to buy some, remember that this experiment was not performed under fully-controlled, laboratory conditions, and we were working with too small a group to prove that the placebo caused an increase in physical performance. But what we can say is that we couldn’t find any correlation between ketone supplements and an increase in physical performance in this experiment. According to Brianna Stubbs, some of the work currently being done on new kinds of ketone salts is starting to show more promise in relation to physical performance, so there may be better news on this down the line.
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).
Athletic performance benefits: The use of exogenous ketone supplements for bettering physical/athletic performance is promising for several reasons. Firstly, taking exogenous ketones (particularly BHB salts) induces acute nutritional ketosis for upwards of eight hours, mimicking fasting physiology (e.g. increases fat burning, insulin sensitivity, etc.).
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 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.
At the same time, research suggests that getting as much of your calcium from your diet, rather than supplements is a good idea. For instance, there is some evidence that the calcium intake from food is better for bone mineral density than the same calcium intake from supplements. Foods that are high in calcium include dairy, leafy green vegetables, fish with edible bones, tofu made with calcium sulfate, and calcium-fortified foods and beverages.
As I mentioned before, this was by no means a scientific experiment carried out under lab conditions, and this means we can only draw tentative conclusions from any of the data. Nonetheless, carrying out the testing in the way described above should give most people a good idea of how well the ketone supplements show the noticeable benefits they are marketed to have and provide a clear enough basis for a decision on whether or not to buy them.
Getting enough sleep not only helps in the production of growth hormones vital for muscle growth, but it plays a particular role as already discussed. If you’re intermittently fasting then sleep is crucial is helping you sustain the fast. 6-10 hours of your day will be dedicated to sleep, helping you to reboot and not think about food during this time. That means less time for you to actually be fasting! Stress is another factor – if we don’t get enough sleep, we’ll tend to feel more stress and agitation throughout the day. Ensuring that we’re well rested plays a huge part in keeping down cortisol levels so that are insulin and blood sugar levels don’t spike.
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.’
The blood levels of BOHB that can be achieved with the salts or ester formulations are in the 1-3 mM range, similar to what can be achieved with a well-formulated ketogenic diet in insulin sensitive humans, but well below levels achieved after a 4-7 days of total fasting (Owen 1969). In more insulin resistant humans, the ester formulation may deliver higher blood levels than a sustainable diet (as opposed to short term fasting). For example, in the Virta IUH Study of over 200 patients with type 2 diabetes, blood ketone mean levels were 0.6 mM at 10 weeks and 0.4 mM after 1 year.
I had the chance to interview Dr. Ryan Lowery, Ph.D. about this in person. He performs some (not peer-reviewed) research on different brands of ketone salts and is listed as one of the “specialists” on Prüvit’s website. He suggested that we had perhaps ran the tests too long after the supplements were taken, stating that blood ketones tend to peak at 30 minutes. This is, however, not what Prüvit themselves state in their article on the 59-minute test, or the promise to reach ketosis in 60 minutes on the Kegenix Prime packaging. Plus, do you really want to spend up to $390/month on a product that gives you the benefits of ketosis for half an hour?
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.
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
Every 7 days, animals were briefly fasted (4 h, water available) prior to intragastric gavage to standardize levels of blood metabolites prior to glucose and βHB measurements at baseline. Baseline (time 0) was immediately prior to gavage. Whole blood samples (10 μL) were taken from the saphenous vein for analysis of glucose and βHB levels with the commercially available glucose and ketone monitoring system Precision Xtra™ (Abbott Laboratories, Abbott Park, IL). Blood glucose and βHB were measured at 0, 0.5, 1, 4, 8, and 12 h after test substance administration, or until βHB returned to baseline levels. Food was returned to animals after blood analysis at time 0 and gavage. At baseline and week 4, whole blood samples (10 μL) were taken from the saphenous vein immediately prior to gavage (time 0) for analysis of total cholesterol, high-density lipoprotein (HDL), and triglycerides with the commercially available CardioChek™ blood lipid analyzer (Polymer Technology Systems, Inc., Indianapolis, IN). Low-density lipoprotein (LDL) cholesterol was calculated from the three measured lipid levels using the Friedewald equation: (LDL Cholesterol = Total Cholesterol - HDL - (Triglycerides/5)) [51, 52]. Animals were weighed once per week to track changes in body weight associated with hyperketonemia.
Hi Rob thanks so much, many people experience inconclusive results from the pee strips, as the ketone concentration in our pee is a measure of ketones not being used by the body. Basically the overflow or unused ketones. As our body becomes more adapted to using ketones, there will be less in our urine. It’s tough to keep the variable constant of how hydrated you are across many pee tests. Don’t be discouraged by pee test results. We have had many times where our blood tests show 1-3mmol/dl BHB but our pee test showed no results. Definitely keep testing (consider using a precision Xtra) and changing the dose to suit your needs. Hope this is helpful!
To determine the reason for the differences in blood d-βHB concentration, the KE and KS drinks were analyzed for enantiomeric purity. The KE contained >99% of the d-isoform, whereas ~50% of the KS βHB was the l-isoform (Figure (Figure1D).1D). Plasma samples from participants who consumed the high dose KS drink (n = 5) were analyzed to reveal higher l-βHB than d-βHB, the total βHB Cmax being 3.4 ± 0.2 mM (Figure (Figure1E),1E), with a total βHB AUC of 549 ± 19 mmol.min. After 4 h, plasma l-βHB remained elevated at 1.9 ± 0.2 mM; differences in urinary excretion of the two isoforms could not explain this observation as both d- and l-βHB were excreted in proportion to their blood AUCs (Figure (Figure1F).1F). Therefore, in order to determine the time required for l-βHB elimination, a follow-up experiment was undertaken in which subjects (n = 5) consumed 3.2 mmol.kg−1 of βHB as KE and KS with hourly blood and breath sample collection up to 4 h, plus additional samples at 8 h and 24 h post-drink. l-βHB was found to be 1.1 ± 0.1 mM at 4 h, and 0.7 ± 0.2 mM after 8 h, but undetectable after 24 h (Figure 1G). Low amounts of d-βHB (0.3 ± 0.1 mM) were present at 24 h, presumably due to endogenous production. Both ketone drinks significantly increased breath acetone concentration, but at a slower rate than blood d-βHB, reaching a peak after 3 h that was twice as high following the KE (87 ± 9 ppm) than the KS (44 ± 10 ppm), suggesting that d-βHB was readily converted to acetone, but l-βHB was not (p < 0.005, Figure Figure1H1H).
Participants refrained from alcohol and caffeine for 24 h prior to each visit AND were asked to consume a similar meal the night before each visit. All studies were carried out at the University of Oxford Human Physiology Laboratories and started at 0800 h following an overnight (>8 h) fast, with a minimum of 72 h between visits. Visit order was randomized prior to commencement by an administrative investigator using a pseudo-random number generator to produce a list of combinations of visit order, which were then allocated based on order of enrolment by a different investigator.
Most people know that you can lose weight by consuming fewer carbs and a lot more protein. However, it's very important that you watch your protein intake carefully if you want to achieve ketosis quickly. There needs to be a balance in the amount of protein you are consuming, since too much of it is not going to be beneficial for you. What you need to remember is that this process is all about getting the right balance of fats, proteins, magnesium, salts, etc., to get your body into ketosis faster.
All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.
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