Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB.
Lots of good info but some things are just plain wrong. It takes 2 days max to get into ketosis if you stop eating carbs. Your body can only store roughly 2 days worth of glycogen. When those stores are exhausted your body will immediately turn to fat. It may take a week or several weeks to get “keto adapted” but it simply won’t ever take you more than 2 days to get into a state of ketosis.
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).
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)
Ketone Esters: These are not normally found in the body, but exogenous ketone esters convert into BHB once it is in the body. They are also synthetically (lab) made compounds that link an alcohol to a ketone body, which can then be metabolized by the liver into a ketone. They are like ketone salts on steroids as they have 5-10 time more BHB per serving/maximum daily intake than ketone salts. To date, pure ketone esters have been very expensive to produce and have only been available to researchers, elite athletes (Tour de France cyclists), and the US Department of Defense (people have spent more than $20,000 to have an independent lab produce a single serving!).
Ketones are naturally slightly acidic, so the combination of BHB with sodium acts as a bit of a buffer to this acidity. Ketones will also naturally act as a diuretic, so you lose salt, potassium calcium and magnesium, and it is generally encouraged to increase sodium intake with ketones. The addition of sodium to the product will replenish this salt loss.
As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. Without exception, every time I ingested these compounds (which I’ve probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake. (At some point I will also write a post on Alzheimer’s disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)
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).
We sampled each of the 3 flavors and also mixed in the available Ketōstax and this supplement tasted better than any other we had tried. Ketōnd costs $79.95 for 30 servings which is about $2.67 per serving – which is less than half the price of the leading competitor. Ketōnd’s label and ingredients are 100% transparent, so they disclose everything that is in the supplement – which is only ketones. What we really liked about Ketōnd is that it isn’t part of some Multi Level Marketing company so there are no obligations.
Human's ability to produce and oxidize ketone bodies arguably evolved to enhance survival during starvation by providing an energy source for the brain and slowing the breakdown of carbohydrate and protein stores (Owen et al., 1967; Sato et al., 1995; Marshall, 2010). The brain is normally reliant on carbohydrate as a substrate, being less able to metabolize lipids, despite adipose tissue representing a far larger energy store than muscle and liver glycogen. Therefore, during starvation, lipids are used for hepatic ketogenesis and, via ketone bodies, lipids sustain the brain. Endogenous production of the ketone bodies, d-β-hydroxybutyrate (βHB) and acetoacetate (AcAc), increases slowly, driven by interactions between macronutrient availability (i.e., low glucose and high free fatty acids) and hormonal signaling (i.e., low insulin, high glucagon and cortisol). Produced continuously under physiological conditions, blood ketone concentrations increase during starvation (Cahill, 1970), when consuming a “ketogenic” (low carbohydrate, high-fat) diet (Gilbert et al., 2000) or following prolonged exercise (Koeslag et al., 1980).
You may wonder why we are emphasizing on using these specific oils. Well, this is because the extra virgin oil is an unprocessed form, and contains lauric acid that is antimicrobial in nature and is good for brain health. (This is the same lauric acid that is naturally found in breast milk as well.) Its antibacterial property also indirectly supports the growth of Candida that keep your gut healthy.
My two cents: I wouldn’t take ketone supps if not on some sort of low(ish) carb diet because the idea of high levels of BOTH fuels (ie, ketones AND glucose) doesn’t seem physiologically appropriate… more like a recipe for disaster, and by “disaster,” I mean “out-of-control production of Reactive Oxygen Species” — this might not matter if you’re an athlete looking for a quick performance boost, because the fuels are going to be cleared rather quickly… not so much if you’re a desk jockey.
Fasting blood samples were collected prior to all interventions. Following consumption of study drinks (details below), blood, expired gas and urine samples were collected at regular intervals for 4 h. Water was freely permitted and participants remained sedentary at the test facility throughout the visit. A subset of participants returned for samples 8 and 24 h after the ketone drinks (Study 1).
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 second ketone ester compound was developed at the University of South Florida. This is a diester of AcAc and BDO. In rodents, this ketone ester raises blood D-BHB to 1-4 mM and blood AcAc to up to 5 mM.19 There is one published study of this ketone ester in humans; results showed a 2% decrease in 31 km cycling time trial performance.16 This may be due to the high rate of side effects of this ester studied. Other factors may have been low levels of BHB (<2 mM), the short, high-intensity time trial used, or the use of AcAc vs. BHB.
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).
If you've tried this type of diet before, or if you've done some research about it beforehand, then you should know that these ten tricks are necessary to get into a ketogenic state quickly, but you will be surprised at the number of people who actually jump on the ketogenic bandwagon without knowing any of the basics first. Remember: A good working knowledge coupled with an effective meal plan can go a long way.
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
Humans in the hunter-gatherer era survived thanks to metabolic flexibility — the body’s ability to use different fuels for energy depending on the nutrients available. This adaptation was vital during a time when the source, quantity, and frequency of food was uncertain[*]. Most of the time, people were fasting, so their bodies ran on ketones, not glucose.
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