2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.
Sometimes waiting for your body to make the switch from carbohydrate metabolism to beta hydroxybutyrate metabolism (aka ketosis) can be an uncomfortable and lengthy process. Another way to get beta hydroxybutyrate into your system so your body is using “clean” energy is by taking it supplementally or through nutrition. A betahydroxybutyrate supplement is what can be used in this scenario. This is an exogenous ketone. Exogenous means you get it from outside of your body. Think EX = exit = outside.
Supplemental BHB’s are ideal for people new to the ketogenic way of eating. The changes that happen in your brain and body when adapting to a VLC diet are both immediate and profound. For example, our kidney’s start processing minerals salts much more efficiently. Ironically, after years of being advised to decrease our intake of salt (sodium), it turns out that for people transitioning away from the Standard American Diet (SAD diet) towards a lower carb or ketogenic diet there is actually a need to increase dietary mineral salts such as potassium, sodium, magnesium and calcium. During the process of becoming keto-adapted, it is very important to increase your intake of these essential minerals, in order to prevent the onset of unpleasant symptoms (known as “keto flu”).
The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.
Glucose and BHB went down slightly throughout the effort and RQ fell, implying a high rate of fat oxidation. We can calculate fat oxidation from these data. Energy expenditure (EE), in kcal/min, can be derived from the VO2 and VCO2 data and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ gives us a good representation of how much of the energy used during the exercise bout was derived from FFA vs. glucose—in this case about 87% FFA and 13% glucose. So fat oxidation was approximately 12.7 kcal/min or 1.41 g/min. It’s worth pointing out that “traditional” sports physiology preaches that fat oxidation peaks in a well-trained athlete at about 1 g/min. Clearly this is context limited (i.e., only true, if true at all, in athletes on high carb diets with high RQ). I’ve done several tests on myself to see how high I could push fat oxidation rate. So far my max is about 1.6 g/min. This suggests to me that very elite athletes (which I am not) who are highly fat adapted could approach 2 g/min of fat oxidation. Jeff Volek has done testing on elites and by personal communication he has recorded levels at 1.81 g/min. A very close friend of mine is contemplating a run at the 24 hour world record (cycling). I think it’s likely we’ll be able to get him to 2 g/min of fat oxidation on the correct diet.
Ketogenic Diets and Physical Performance – Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis. (http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-1-2)
In fact this was one of the biggest surprises I had when exploring ketosis. For years I have been following a cyclical lower carb diet. For years I wouldn’t consume a carb until later in the afternoon (ala Carb Backloading style). After eating 5 days without any carbs I tested my ketone levels… they were 0.1 mmol. This reading was done first thing in the morning (10 hours fasted) after 5 days without a carb in my diet.
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.
It's also a smart idea to start slowly with this supplement. We can thank Dave Asprey for the term “disaster pants” which has been used by those who try MCT oil at too high a dose when they first start using it. There is a chance that you can experience the same unpleasant gastrointestinal effect with exogenous ketones if you start with too high a dose, or if you maintain a higher carbohydrate diet while using this supplement. Used in appropriate doses, it gets absorbed through your stomach into your liver, then sent out to the rest of your body.
Ketosis supplements made in poor quality have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men. Women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is essential to know what combination of compounds you are consuming while you are on this very strict diet. The wrong balance can mess with you in the long term and won't give you the results that you are looking for.
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)
Alright, first of all, I tried every combination available for this product. I really loved the idea of adding it to my morning iced coffee with MCT, 1 tbs of heavy cream and stevia. To be honest, my morning coffee is one of my favorite things throughout my day and I was very dissppointed when it didn’t taste *exactly* like an iced mocha. I found it to be very bitter and tough to finish. Not to mention it was ruining my love for my morning coffee time.
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).
Emerging evidence supports the therapeutic potential of the ketogenic diet (KD) for a variety of disease states, leading investigators to research methods of harnessing the benefits of nutritional ketosis without the dietary restrictions. The KD has been used as an effective non-pharmacological therapy for pediatric intractable seizures since the 1920s [1–3]. In addition to epilepsy, the ketogenic diet has elicited significant therapeutic effects for weight loss and type-2 diabetes (T2D) . Several studies have shown significant weight loss on a high fat, low carbohydrate diet without significant elevations of serum cholesterol [5–12]. Another study demonstrated the safety and benefits of long-term application of the KD in T2D patients. Patients exhibited significant weight loss, reduction of blood glucose, and improvement of lipid markers after eating a well-formulated KD for 56 weeks . Recently, researchers have begun to investigate the use of the KD as a treatment for acne, polycystic ovary syndrome (PCOS), cancer, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI) and Alzheimer’s disease (AD) with promising preliminary results [14–26].
A meal high in carbohydrate and calories significantly decreased peak d-βHB by ~ 1 mM (Figure (Figure4A)4A) and reduced the d-βHB AUC by 27% (p < 0.001, Figure Figure4B).4B). There were no significant changes in d-βHB Tmax (fed = 73 ± 6 min vs. fasted 66 ± 4 min). Despite the differences in d-βHB kinetics after the meal, there were no effects of food on urinary ketone excretion (Figure (Figure4C),4C), plasma AcAc (Figure (Figure4D)4D) or breath acetone (Figure (Figure4E)4E) following KE ingestion. Plasma AcAc kinetics followed a similar time course to d-βHB, with the ratio of blood d-βHB: AcAc being 6:1 when KE drinks were consumed whilst fasted, and 4:1 following the meal. As observed in Study 1, breath acetone concentrations rose more slowly than blood ketone concentrations, reaching a plateau at 150 min and remaining elevated for at least 4 h (Figure (Figure4E4E).
Ketone supplementation did not affect the size of the brain, lungs, kidneys or heart of rats. As previously mentioned, the rats were still growing during the experimental time frame; therefore, organ weights were normalized to body weight to determine if organ weight changed independently to growth. There could be several reasons why ketones influenced liver and spleen weight. The ratio of liver to body weight was significantly higher in the MCT supplemented animals (Fig. 5). MCTs are readily absorbed in the intestinal lumen and transported directly to the liver via hepatic portal circulation. When given a large bolus, such as in this study, the amount of MCTs in the liver will likely exceed the β-oxidation rate, causing the MCTs to be deposited in the liver as fat droplets . The accumulated MCT droplets in the liver could explain the higher liver weight to body weight percentage observed with MCT supplemented rats. Future toxicology and histological studies will be needed to determine the cause of the observed hepatomegaly. It should be emphasized that the dose in this study is not optimized in humans. We speculate that an optimized human dose would be lower and may not cause hepatomegaly or potential fat accumulation. Nutritional ketosis achieved with the KD has been shown to decrease inflammatory markers such as TNF-α, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46], which may account for the observed decrease in spleen weight. As previously mentioned, Veech and colleagues demonstrated that exogenous supplementation of 5 mM βHB resulted in a 28 % increase in hydraulic work in the working perfused rat heart and a significant decrease in oxygen consumption [28, 41, 42]. Ketone bodies have been shown to increase cerebral blood flow and perfusion . Also, ketone bodies have been shown to increase ATP synthesis and enhance the efficiency of ATP production [14, 28, 40]. It is possible that sustained ketosis results in enhanced cardiac efficiency and O2 consumption. Even though the size of the heart did not change for any of the ketone supplements, further analysis of tissues harvested from the ketone-supplemented rats will be needed to determine any morphological changes and to understand changes in organ size. It should be noted that the Harlan standard rodent chow 2018 is nutritionally complete and formulated with high-quality ingredients to optimize gestation, lactation, growth, and overall health of the animals. The same cannot be said for the standard American diet (SAD). Therefore, we plan to investigate the effects of ketone supplements administered with the SAD to determine if similar effects will be seen when the micronutrient deficiencies and macronutrient profile mimics what most Americans consume.
I carried out a survey among Diet Doctor users as background research to the experiment (a big thank you to the 638 people who responded!). In the survey, 28% of the respondents reported that they do take ketone supplements. The top four benefits that these respondents reported experiencing were increased energy, improved focus/cognition, reduced hunger and weight loss.
This is an excellent resource. Thank you for all the work and resources you found. i had never even heard of Adkins 72. I am keto but I always let Sunday be my high Carb cheat day.So im learning from this blog how to get back in ketosis in 24 hours after my 4pm meal on Sunday The Lords & family day. So im 25hr fasting. I would like to reference this article on my blog, thanks for helping me on my 100 lb lost journey.
If you are new to ketosis and don’t know much about it, it is a metabolic state, where your body preferentially uses ketones (instead of glucose) for energy. This can lead to a host of different health benefits. If you’d like to learn more about ketosis, what ketones are, and how to benefit from these, feel free to read through our guides: What is Ketosis? What is the Ketogenic Diet? What Are Ketones?
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.
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.
There are many top-rated exogenous ketone supplements, which is a great resource to help get your body to adapt faster and produce at a high-performance level, but you need to be careful how they can effect you and your energy levels and your general mood each day, so it’s important to check with your local physician and be safe about it. Remember that when you switch over to this diet, you must maintain high sodium levels during the process. It is recommended to add more 'keto salt' to your daily intake, starting off gradually and increasing it to as much as 500g a day. You need to add salt and electrolytes to your routine, because a person can lose levels through their urine, which causes your body to become more dehydrated and can leave you feeling a little sick and weak if you don't have the balance properly set up. Most exogenous ketone supplements we found have quite a bit of sodium in their ingredients, which helps you reach the level of salt intake you need each day. It is important to understand how this whole process works before even thinking about tackling it yourself. This is why you should consult with a professional to seek out advice and address any concerns that you may have before getting started.
Over the 28-day experiment, ketone supplements administered daily significantly elevated blood ketone levels without dietary restriction (Fig. 2a, b). Naturally derived ketogenic supplements including MCT (5 g/kg) elicited a significant rapid elevation in blood βHB within 30–60 min that was sustained for 8 h. BMS + MCT (5 g/kg) elicited a significant elevation in blood βHB at 4 h, which was no longer significant at 8 h. BMS (5 g/kg) did not elicit a significant elevation in blood βHB at any time point. For days 14–28, BMS + MCT (10 g/kg) and MCT (10 g/kg) elevated blood βHB levels within 30 min and remained significantly elevated for up to 12 h. We observed a delay in the peak elevation of blood βHB: BMS + MCT peaked at 8 h instead of at 4 h and MCT at 4 h instead of at 1 h. Blood βHB levels in the BMS group did not show significant elevation at any time point, even after dose escalation (Fig. 2a). Synthetically derived ketogenic supplements including KE and BD supplementation rapidly elevated blood βHB within 30 min and was sustained for 8 h. For the rats receiving ketone supplementation in the form of BD or the KE, dosage was kept at 5 g/kg to prevent adverse effects associated with hyperketonemia. The Precision Xtra™ ketone monitoring system measures βHB only; therefore, total blood ketone levels (βHB + AcAc) would be higher than measured. For each of these groups, the blood βHB profile remained consistent following daily ketone supplementation administration over the 4-week duration. (Fig. 2b).
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).
I’ve tried this, got a few bags of one ketone salts bound to mostly potassium and another one bound to calcium. As for working out, I find that consuming 15-20 grams of glucose ( dextrose ) 30 minutes before either a HIIT or a heavy lifting session gives me a much, much bigger boost than ketones. so they just sit in my cupboard. I also got spooked about the amount of potassium i’d consume in one go ( don’t particularly fancy a cardiac arrest ). I find it a bit useful when I have a big meeting or something else that requires super concentration and I’m fasting, other than that – it’s pretty useless. I’d probably use more of it if I could find a formula that’s mostly sodium/magnesium based rather than potassium and/or calcium.
The famous keto-breath is powerful enough to throw shade on your increasingly ripped rig. The mouth-based ketones are released when your body scalds fat are responsible for the pong. Going into ketosis by changing your diet means your body doesn’t have carbs as a fuel source, so you’re using fats and proteins for energy, which fuels the potency of the fireworks seeping from your grill. The same can happen when taking supplements, but not by the same degree – proving that changing your diet it obviously a more potent fat burning tool. A lot of people also report gastric distress, so you could offend those you’re co-habituating with. What’s more, they can have a slight diuretic effect, which can deplete your magnesium, potassium and sodium stores, so make sure your levels are topped up when you’re out for a extra long exercise stint. Research in Nutrition and Metabolism on animals, found there were no negative side effects, but whether this extends to humans is still up for discussion. Fortunately, you’re more likely benefit from the upsides such as improved endurance, appetite suppression and fat burning.
For the past few million years, the only way for humans to make use of ketones for fuel was to restrict carbohydrates low enough and long enough to induce the liver to make them. This is admittedly hard for many people to do in a world that still believes that dietary carbs are good and fats are bad. An emerging alternative is to consume ketones as a dietary supplement. The research into how these function in the body and what benefits they can confer remains early stage, but there are already a number of such products available for sale. In this section, we will discuss how exogenous ketones affect blood ketone levels, and how they may influence health and disease compared to ketones produced within the body.
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