Intellectual property covering uses of dietary ketone and ketone ester supplementation is owned by BTG Ltd., the University of Oxford, the National Institute of Health and TΔS Ltd. Should royalties ever accrue from these patents, KC and PC, as inventors, will receive a share of the royalties under the terms prescribed by the University of Oxford. KC is a director of TΔS Ltd., a company spun out of the University of Oxford to develop and commercialize products based on the science of ketone bodies in human nutrition. At the time of data collection and manuscript preparation, BS was an employee of TΔS Ltd., funded by the Royal Commission for the Exhibition of 1851. SH is an employee of NTT DOCOMO, Inc. (Japan). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Most supplements rely on BHB as the source of their exogenous ketone bodies. BHB is converted to acetoacetic acid with a small quantity converted to acetone through a acetoacetate decarboxylase waste pathway. Some of the acetoacetic acid will enter the energy pathway using beta-ketothialase, which converts acetoacetic acid to two Acetyl-CoA molecules (see diagram below2).
Beta hydroxybutyrate floats around in your blood, and importantly, can cross different barriers to be able to be turned into energy at all times. One of the most important areas where this happens is in the brain. The blood-brain barrier (BBB) is usually a very tightly regulated interface that doesn’t allow the transfer of many molecules, but since BHB is such a rock star and so hydrophilic, your brain knows to let it in so it can bring energy to the party at any time. This is one of the main reasons why increased levels of ketosis lead to improved mental clarity, focus and reduction in neurodegenerative diseases.
In Study 2 a Student's unequal variance t-test with equal SD was used to compare urine βHB concentrations. Additionally, a linear mixed effects model was constructed to estimate partitions of variance in R, using the lme4 and blme packages (Chung et al., 2013; Bates et al., 2015). Feeding state and visit number were fixed effects in this model, and inter-participant variability was a random effect. Inter-participant variability was calculated according to the adjusted generalized R2 metric (as proposed by Nakagawa and Schielzeth, 2013), to partition variance between the fixed effects of feeding, inter-participant variability, and residual variability. The coefficient of variation for βHB Cmax and AUC were calculated using the method of Vangel (1996).
One other thing I must point out is also that we are talking about being in ketosis and not being fully keto adapted. You enter ketosis when your body starts producing ketones above a specified level, being fully keto adapted means that your body is full adapted to use fat as your primary energy source and that the production of certain enzymes in your body is fully adapted. This doesn’t happen in one day and it takes about 1 month on average to be fully keto adapted. But we are not looking for this as we just want to end the most unpleasant period and to start losing weight.
You must realise that our bodies are lazy and switching to a new energy source means hard work, that means that your body will not do this easily and you basically have to force it. One way to speed up this process is to put your body into fight or flight mode. My preferred controlled exercise to do this is to have a high intensity workout followed immediately by a cold shower. I am describing it in the article to go slowly, but in this case it will actually be beneficial if you can force your self to go straight into a cold shower and try to stay there at least 2 minutes. One of the benefits of this that your body will produce the hormone noradrenaline. Obviously this is something for people in perfect health. Please advice your doctor before you want to take cold showers.
Plus, take a look at this promotional video from Prüvit. It claims that “ketones make the fat melt off your body”, which is simply not true (I’ll get back to this later). It also claims that if you wanted to reach ketosis naturally, you would either need to work out 10x harder and longer or be like one of the “extreme people” who “biohack their bodies” to get into ketosis, which “can take weeks or months”. For me, this is irresponsible. A keto diet can be simple and enjoyable, but this video makes switching to a healthy, real food, keto diet sound extreme and difficult while promoting an easy way out in the form of a drink. And that’s just bad advice.
Even though there is mixed evidence regarding the association between calcium supplementation and cardiovascular events, there may be other reasons to avoid high calcium supplementation. In one of his studies, Dr. Bolland claimed that calcium supplements do not prevent hip fractures. Rather, they may lead to kidney stones, acute gastrointestinal events, and increased risk of myocardial infarction and stroke. Thus, the risks involved with high-calcium supplementation potentially outweigh the benefits.
Intermittent fasting will significantly help the body transition into ketosis as limiting your consumption of food for that many hours will help deplete the system of any excess glucose. It’s a shock to the system and research has shown that daily fasting can have other profound effects aside from weight control such as autophagy, lowering risks of heart disease and diabetes, as well as an improvement in cognitive function. So if you’re still wondering how to get into ketosis in 24 hours, then fasting will surely kick things into gear!
While it usually takes 2-7 days for your body to enter into a state of ketosis on a ketogenic diet, there are a few things you can do to kickstart this process. It isn’t guaranteed but it will assist in the process, and may work in extreme cases. Intermittent fasting, exercise, proper sleep, a strict high-fat-low-carb diet, and supplementation can all help fastened the transition process. Whether you’ve fallen out of ketosis after a cheat weekend or maybe you’re somebody who have just started out on your keto journey – here is how to get into ketosis in 24 hours.
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).
Dominic D’Agostino has two in-depth interviews on The Tim Ferriss Show (Part 1, Part 2). Discussion includes exogenous ketones for mitigating the onset of neurodegenerative diseases, using ketones in place of fasting for chemo-protection, benefits of ketone supplementation when consuming carbohydrates, the risks and potential toxicities of ketones.
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?
With oral ketone supplementation, we observed a significant elevation in blood βHB without dietary restriction and with little change in lipid biomarkers (Fig. 1). Over the 4 week study, MCT-supplemented rats demonstrated decreased HDL compared to controls. No significant changes were observed in any of the triglycerides or lipoproteins (HDL, LDL) with any of the remaining exogenously applied ketone supplements. It should be noted that the rats used for this study had not yet reached full adult body size . Their normal growth rate and maturation was likely responsible for the changes in triglyceride and lipoprotein levels observed in the control animals over the 4 week study (baseline data not shown, no significant differences) [80, 81]. Future studies are needed to investigate the effect of ketone supplementation on fully mature and aged animals. Overall, our study suggests that oral ketone supplementation has little effect on the triglyceride or lipoprotein profile after 4 weeks. However, it is currently unknown if ketone supplementation would affect lipid biomarkers after a longer duration of consumption. Further studies are needed to determine the effects of ketone supplements on blood triglyceride and lipoproteins after chronic administration and as a means to further enhance the hyperketonemia and improve the lipid profile of the clinically implemented (4:1) KD.
North Americans typically live pro-inflammatory, pro-disease lives (think about your everyday: likely sitting in a flexed position for hours on end, not enough natural sunlight, not enough movement, artificial food stuffs, artificial colouring, going to bed late, blue light exposure, less in-person contact with our loved ones, late night snacks, the list goes on and on).
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.
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?
Zenwise Health Keto BHB is an exogenous ketone supplement that features goBHB, an innovative beta-hydroxybutyrate complex that supports the body's fueling processes through nutritional ketosis to promote peak mental and physical performance. Great for reaching ketosis fast, to max out your pre-workout routine, while also promoting overall high-performance, brain function, and maximum endurance. This Keto powder formula features a Raspberry Lemonade flavor that will mix and shake well with any water based drink. Best of all, this BHB is formulated with absolutely no carbs or caffeine for clean energy. Simply mix this BHB powder with water-based drinks or your favorite fruit flavored drink or smoothie, and enjoy.
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).
MCT oil has recently been used to induce nutritional ketosis although it produces dose-dependent gastrointestinal (GI) side effects in humans that limit the potential for its use to significantly elevate ketones (>0.5 mM). Despite these limitations, Azzam and colleagues published a case report in which a 43-year-old-man had a significant decrease in seizure frequency after supplementing his diet with 4 tablespoons of MCT oil twice daily . An attempt to increase his dosage to 5 tablespoons twice daily was halted by severe GI intolerance. Henderson et al. observed that 20 % of patients reported GI side effects with a 20 g dose of ketogenic agent AC-1202 in a double blind trial in mild to moderate Alzheimer’s patients . We visually observed similar gastrointestinal side effects (loose stools) in the rats treated with MCT oil in our study. Rats were closely monitored to avoid dehydration, and gastric motility returned to normal between 12–24 h. Interestingly, the BMS + MCT supplement elevated βHB similarly to MCT oil alone, without causing the adverse gastrointestinal effects seen in MCT-supplemented rats. However, this could be due to the fact in a 10 g/kg dose of BMS + MCT, only 5 g/kg is MCT alone, which is less than the 10 g/kg dose that elicits the GI side effects. This suggests that this novel combination may provide a more useful therapeutic option than MCT oil alone, which is limited in its ability to elevate ketones in humans.
Neuroprotective benefits: A natural part of the aging process is neurodegeneration, which is largely responsible for cognitive defects like Alzheimer’s disease. Recent research suggests that exogenous ketone supplementation can drastically slow neurodegeneration and the resulting decrease in mental function. However, the mechanism behind this finding remains to be elucidated; though, researchers suggest exogenous ketones act to reduce brain inflammation. Glucose, on the contrary, may actually accelerate inflammatory response in the brain.
There are three types of ketones produced when you’re on ketogenic diet: acetoacetate, beta-hydroxybutyrate (BHB), and acetone. The kinds that you’ll find in your supplements are BHB because your body can readily use and absorb them. This means that not all ketones are created equal and there are several different types, each with unique properties that are worth considering when shopping.
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.
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.
When you are in a state of ketosis, the body turns fatty acids into ketones - these appear as beta-hydroxybutyrate in the blood. Measuring blood ketones is regarded as the gold standard and most accurate way to track ketone levels. Testing this way can be expensive, its can cost up to $3 a strip, so if you're testing multiple times a day it can get pricey.
So long long does it take to get into ketosis? This transition could take anywhere from 48 hours to one week. The length in time will vary depending upon your activity level, lifestyle, body type and carbohydrate intake. There are several ways you can speed up this process, like intermittent fasting, drastically decreasing your carb intake and supplementation.
I’m getting an increasing number of questions about exogenous ketones. Are they good? Do they work for performance? Is there a dose-response curve? If I’m fasting, can I consume them without “breaking” the fast? Am I in ketosis if my liver isn’t producing ketones, but my BOHB is 1.5 mmol/L after ingesting ketones? Can they “ramp-up” ketogenesis? Are they a “smart drug?” What happens if someone has high levels of both glucose and ketones? Are some products better than others? Salts vs esters? BHB vs AcAc? Can taking exogenous ketones reduce endogenous production on a ketogenic diet? What’s the difference between racemic mixtures, D-form, and L-form? What’s your experience with MCTs and C8?
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