Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. – Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy. (http://www.ncbi.nlm.nih.gov/pubmed/15123336)
There is so much talk about the benefits of a ketogenic diet and its ability to improve fat burning, brain health, energy and anti-aging. The main units of energy on a ketogenic diet are ketone bodies, of which beta hydroxybutyrate (BHB) is the main player! This article will go over the health benefits of BHB and exogenous ketones. Additionally, this article will cover strategies on using exogenous ketones in your daily life.
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!
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).
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.
If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.
Best exogenous ketone I've tried (bhb). I've been eating a keto diet since Feb 2017 and notice athletic/ mental improvements with all the products I've tried but this has the best flavor by far . Bhb ranges from jet fuel (nutricost 4-1) to a citrus lemonade and this is the later. This is my goto for sure! Ketocana worked well and tastes ok but I prefer the taste of keto bhb
Effects of ketone supplementation on organ weight: Data is represented as a percentage of organ weight to body weight. a, b, d, f Ketone supplements did not significantly affect the weight of the brain, lungs, kidneys or heart. c Liver weight was significantly increased as compared to body weight in response to administered MCT ketone supplement compared to control at the end of the study (day 29) (p < 0.001). e Rats supplemented with BMS + MCT, MCT, and BD had significantly smaller spleen percentage as compared to controls (p < 0.05, p < 0.001, p < 0.05). Two-Way ANOVA with Tukey’s post-hoc test; results considered significant if p < 0.05. Error bars represent mean (SD)
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Some common short-term effects that some people experience in the early stages of the process are excessive thirst, fatigue and keto constipation. These minor side-effects occur due to a sudden change to a persons diet, but as I said, once your body starts to adjust to the process, you will start to feel normal again, if not better than before you started. We understand that constipation isn't exactly fun, but it's a small price to pay to experience the long-term health benefits.
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.
Full disclosure: after carrying out the background research, I was already, as you might imagine, feeling a little less neutral about these products. You may have noticed a hint of that in part 1 of the 2-part video series we made about the project (watch part 2 at the top of this page!). However, and although this was by no means a controlled scientific study under laboratory conditions, we designed the experiment in a very objective way. The aim was to give the supplements the best possible chance of showing the benefits they are claimed to have.
I simply use this to attempt to reduce the symptoms of the "keto-flu" when I'm entering ketosis after blowing my carbs out. The holidays are particularly bad for falling off the keto band-wagon. I've used this three times now to transition back into ketosis and I can report that it does seem to reduce the effects of the keto flu (headache, weakness) that I'd normally experience transitioning back into a low-carbohydrate diet. I typically take it for 3 days and then stop because by that time I'm in ketosis again, but I'd imagine you could take it longer.
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.
Ketones naturally exist in the body, being created during the process of fat metabolism and are therefore safe to consume even during pregnancy or breastfeeding. Supplements such as Ketologie’s PROBHB are simply providing ketones from an external (exogenous means literally ‘outside of the body’) source. However, if you suffer from any medical conditions and/or are on medications, it is always advisable to consult your health care provider prior to starting any new nutritional or dietary supplement.
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
While the KetoneAid folks have been seeing tremendous success working with elite athletes to improve athletic performance, I thought it would be interesting to quantify the effects of ketone esters on cognitive performance. For the week prior to taking the ketones, I re-established baseline scores in a number of cognitive testing areas using Lumosity*:
Exogenous ketones are not a magical fat-loss supplement, and to suggest otherwise is both factually incorrect and deliberately misleading. In fact, consuming ketones to excess can hinder rather than help fat loss! Aggressive marketing of exogenous BHB’s has helped to create a myth being believed now by millions – that simply drinking ketones each day will somehow magically melt away the pounds. The metabolic fact that unscrupulous marketers do not point out is that dietary fat (plate fat; or fat/ketones you ingest) will be burned before stored fat (body fat). So, whilst exogenous ketones can help you to mitigate hunger (and therefore help you achieve a caloric deficit) – and although they also have many other benefits (detailed below); they are not a magic wand that you can wave to achieve weight or fat loss and should not be marketed as such.
The effects of the two exogenous ketone drinks on acid-base balance and blood pH were disparate. In solution the ketone salt fully dissociates (giving a total of 3.2–6.4 g of inorganic cation per drink), allowing βHB− to act as a conjugate base, mildly raising blood and urine pH, as seen during salt IV infusions (Balasse and Ooms, 1968; Balasse, 1979). Urinary pH increased with the salts as the kidneys excreted the excess cations. In contrast, KE hydrolysis in the gut provides βHB− with butanediol, which subsequently underwent hepatic metabolism to form the complete keto-acid, thus briefly lowering blood pH to 7.31. Electrolyte shifts were similar for both KE and KS drinks and may have occurred due to βHB− metabolism, causing cellular potassium influx and sodium efflux (Palmer, 2015).
There are a couple factors that will make this look much more viable and achievable. For example, if you were to skip breakfast and have your first meal at 12PM, you could eat up until 8PM. This will also mean that dinner needs to be eaten slightly earlier. But let’s not forget about the fact that if we were to combine this with the 6-10 hours of sleep that you would normally have each night, that’ll take up the majority of your fasting period. Obviously, you’re not restricted to these hours, as everyone has a different schedule. Doesn’t sound as bad as you initially thought? Well let’s make it even more enticing! During your fasting hours, and this is extremely helpful during mornings up until you can have your first meal, non-caloric beverages such as tea and coffee can help starve away those hung pangs. Just make sure you’re taking these drinks on it’s own, without any added sugar or milk. There are many variations of intermittent fasting with the most common being 16/8. But depending on your schedule, there are other options advocated such as 20/4, 22/2, and if you’re crazy enough and can eat a full day’s worth of calories in one sitting then there is also OMAD (one meal a day).
So, now that we've established that purchasing BHB supplements directly from the manufacturer is the way to go. Now, let's talk about which ketogenic product you should be buying in the stores. Well, if you read our review about the different exogenous ketone supplements, you will also know that Perfect Keto is rated #1 on our list which was a pretty close race but it came out on top after all the tests that we've performed on all the different products.
For example, the popular Raspberry Ketones supplement is far different than what we have been discussing in this article. Raspberry ketones are unrelated to the ketones that are produced in the body and are not the same as the ketone salts that have been covered above. There are some limited studies that indicate raspberry ketones may be helpful for weight loss, but they are inconsistent. Raspberry ketones are the molecules that give raspberries their scent and flavor, and in some cases, aren’t even derived from raspberries at all.
The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat . The macronutrient ratio of the KD induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) in the blood. Acetone, generated by decarboxylation of AcAc, has been shown to have anticonvulsant properties [28–32]. Ketone bodies are naturally elevated to serve as alternative metabolic substrates for extra-hepatic tissues during the prolonged reduction of glucose availability, suppression of insulin, and depletion of liver glycogen, such as occurs during starvation, fasting, vigorous exercise, calorie restriction, or the KD. Although the KD has clear therapeutic potential, several factors limit the efficacy and utility of this metabolic therapy for widespread clinical use. Patient compliance to the KD can be low due to the severe dietary restriction - the diet being generally perceived as unpalatable - and intolerance to high-fat ingestion. Maintaining ketosis can be difficult as consumption of even a small quantity of carbohydrates or excess protein can rapidly inhibit ketogenesis [33, 34]. Furthermore, enhanced ketone body production and tissue utilization by the tissues can take several weeks (keto-adaptation), and patients may experience mild hypoglycemic symptoms during this transitional period .
Exogenous ketones can lower appetite during a fast. After an overnight fast, normal weight human subjects either drank a ketone ester supplement or a calorie-matched glucose drink. Compared to the glucose drinkers, the ketone drinkers had lower insulin, lower ghrelin, greater satiety, and less hunger. This can be useful for people trying to extend their fast who don’t want to or can’t yet deal with the hunger. You’re still taking in energy, but the metabolic profile remains similar to that of a fasted person.
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)
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.
I stumbled onto this trend before it even blew up, I have read just about every peer-review journal of the topic, I have trialed as well as tested different methods and keto products (exogenous ketones, MCT oils, pills, etc), and lastly, I have reported and analyzed my performance to share with you all. It hasn't been an easy task, but I have also seen the fruits of the labor, and the fruit is sweet.
I’m fasting (5 days fast, 2 days food) in an effort to aggressively lose weight. For the most part, I’m not doing the water & salt-only kind of fast… as I will also drink coffee & bone broth… as well as take Perfect Keto Base. Would it be “gilding the lily” to also add MCT powder to my coffee? I’m in nutritional ketosis… ranging from 0.8 to 2.0 or thereabouts.
The human studies aren’t quite there yet, but it seems likely that they’d help. A recent human case study found that ketone esters added to the regular diet improved Alzheimer’s symptoms. Animal studies indicate that adding exogenous ketones to a regular lab (read: not ketogenic) diet can reduce seizure activity and improve overall symptoms in epilepsy animal models, reverse early neuronal hyperactivity in Alzheimer’s animal models, and reduce anxiety in rats.
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).
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).
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.
The protocols carried out in these studies were approved by the the South West Frenchay NHS REC (15/SW/0244) (Study 1) and London Queen's Square REC (14/LO/0288) (Study 2 and 3). The studies were carried out in accordance with the recommendations of the Declaration of Helsinki, apart from pre-registration in a database. All subjects gave written informed consent in accordance with the Declaration of Helsinki.
Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.
Exogenous Ketones have been shown in performance studies of both humans and animals to improve metabolic efficiency, which in essence means that your body is using better fuel that burns more efficiently over longer periods of time, and decreases the amount of fuel you need while performing. Where glucose fails (glycogen depletion), ketones pick up the slack!
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.
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.
The salts typically utilize sodium, potassium, calcium, or magnesium as the cation. Because these cations vary in molecular weight and valence (1+ or 2+), the amount of mineral delivered per gram of BOHB varies from 10% for the magnesium salt to 27% for potassium. Given that recommended daily intakes of these various minerals range from a few hundred milligrams up to 5 grams, whereas the daily ketone intake goal to mimic nutritional ketosis blood levels would need to be on the order of 50 grams, achieving this goal with ketone salts would severely challenge human dietary mineral tolerance.
Exogenous ketones are becoming more popular as advancements in scientific research continue to show how they work to improve both health and performance. At first, the only options for delivering exogenous ketones were unpalatable ketone esters; however, exogenous ketones can now be taken in the form of ketone mineral salts that are more palatable and easily blended in water. Making ketone mineral salts involves combining beta-hydroxybutyrate (BHB) with mineral salts such as sodium, calcium, magnesium, or potassium. Before considering whether ketone supplements are a good option, most people immediately look at the salt load, and rightfully so. It is important to take into account the nutritional and health impact of not only the BHB but the minerals that are used to make the product.
There are several ways to approach the “intermittent” part of food restriction. One of the most common is limiting the window in which food is consumed to about eight hours a day. Another is fasting for a full 24 hours once a week, or once a month. Fasting beyond three days can be stressful on the body and should be done with medical advice and supervision.
I noticed for myself that it helps if I add some highly nutritional foods to my diet before I go into ketogenic diet. Adding minerals and vitamins will aid your body in this difficult process and on top of that if you have a deficiency of some sort you will be even more hungry and it will make your transition more difficult, so why make it harder on your self if you can just add some leafy greens to your diet.
I wrote this post at about the same time Germany won the World Cup in Rio de Janeiro in 2014. There’s been a lot of moving and shaking in the world of exogenous ketones since then, not to mention soccer. Looking back on my post, I still consider it relevant in terms of what exogenous ketones possibly can (and cannot) do for performance. In this case, to see if exogenous ketone esters provide me a “boost” by allowing me to do the same amount of work while expending less energy (and work at a relatively lower VO2) compared to no supplementation.
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