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).
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.
Selective attention involves focusing only on relevant information while suppressing the impulse to pay attention to irrelevant distractions. A v-shaped flock of birds are displayed. The center (target) bird points in one direction and is surrounded by birds that either match the target’s direction or do not. The task is to rapidly identify which direction the target bird is pointing.
How did I do this? Simple, I went into a full fast and exercised. What prevents you from entering ketosis is all the glycogen stored in your liver and muscles. Your body can use this glycogen instead of ketones to fuel your brain, so until you deplete your stores of glycogen, you won’t be able to enter ketosis. By eating nothing, you are going to tap into the glycogen to fuel your brain because you are eating 0 grams of carbs and will also be using that glycogen to walk around all day.
Firstly, in a randomized four-arm cross-over study, blood βHB concentrations were compared following ingestion of equal amounts of βHB as a KE or a KS at two doses by healthy volunteers at rest (Study 1; n = 15). Secondly, in a randomized five-arm cross-over study, inter- and intra-participant repeatability of ketosis was examined following ingestion of identical KE drinks, twice whilst fed and twice whilst fasted. As a control, participants also consumed one isocaloric (1.9 kCal.kg−1) dextrose drink (Study 2; n = 16). Finally, blood d-βHB was measured after equal amounts of KE were given as three drinks (n = 12) or a constant nasogastric (NG) infusion (n = 4) (Study 3; total n = 14) over 9 h.
Keep these studies in mind as your body tries to play tricks on you during your first day of fasting. Even after three days of fasting, health complications are highly unlikely. However, it is important to know about the possible issues that can be caused by fasting. If you choose to incorporate fasting into your daily diet, you typically want to eat every day as well. Occasionally going on a longer period of fasting.
If you’ve done any reading about ketosis, you no doubt read at some point that ketosis is a “natural” state. You may have read on a bit more and learned what is meant by that statement or you may have simply skipped ahead to the keto success stories and decided to give it a try. But we’d like to direct your attention back to that little tidbit of information about keto being “natural” for a moment.
You are probably wondering how there could possibly be a benefit to eating less frequently that goes beyond what you are already getting with a ketogenic diet. Restricting carbs and eating enough fat and protein does come with a plethora of health benefits, but when you add intermittent fasting to your lifestyle you can increase energy and reverse aging by harnessing the power of a nobel prize winning process.
Blood, urine, plasma, and breath ketone concentrations following mole-matched ketone ester or isocaloric dextrose drinks in fed and fasted subjects (n = 16) at rest. Data from both of the two study visits in each condition (fed and fasted) completed by an individual are included in the analysis. Values are means ± SEM. (A) Blood d-βHB. (B) AUC of blood d-βHB. (C) Urine d-βHB excretion. (D) Plasma acetoacetate (AcAc). (E) Measured breath acetone (ppm = parts per million). (F,G) Mean d-βHB Cmax and difference between βHB Cmax over two visits when subjects separately consumed two ketone ester drinks in both the fed (F) and fasted (G) state. X axis = mean d-βHB Cmax of the 2 visits (mM), Y axis = difference between d-βHB Cmax in each visit. 95% confidence limits are shown as dotted lines. Significance denoted by: *p < 0.05 fed vs. fasted.
Here we investigated the effects of KE and KS consumption on blood βHB and metabolite concentrations. As we found that KE ingestion delivered a >50% higher plasma concentrations of d-βHB alone, we subsequently determined the reliability and repeatability of ketosis following KE consumption and the effects of concomitant meal ingestion on blood ketone and substrate kinetics. Finally, we determined whether nasogastric infusion could be used for KE administration, given that some patients require feeding in this manner.
Also known as the carb flu, the keto flu is commonly experienced by people who are transitioning to a Ketogenic diet. “Keto flu” is not actually flu but mimics the experience of flu with very similar symptoms. It can happen when someone who has become accustomed to relying primarily on carbohydrates as fuel removes them from their diet. Whilst this is a necessary step towards adjusting from being a sugar-burner to a fat-burner, the sudden change can trigger some unpleasant symptoms, much like withdrawing from an addictive substance. Keto flu symptoms can include drowsiness, nausea, dizziness, achy muscles, mental fogginess and an irritable mood. The good news though, is that most of these experiences relate to dehydration and electrolyte depletion, and so are easily prevented or managed. Simply adding a ¼ - ½ teaspoon of a high quality sea salt or sodium/potassium powder to a glass of water works wonders; however you may still require a separate magnesium supplement; particularly if you are prone to muscle cramps or restless legs. Another popular way to manage your electrolytes is via a good quality bone broth powder. Finally, since BHB’s are normally delivered via a mineral salt base*, keto flu symptoms are easily prevented or reduced by using an exogenous ketone supplement powder.
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).
As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
Neuroprotection: As humans age, the brain becomes more susceptible to neurodegeneration and subsequent conditions such as Alzheimer’s and Parkinson’s disease. Exogenous ketone supplementation appears to ameliorate the typical decline in cognitive function that comes with aging. The likely mechanism for this neuroprotective property is that ketone bodies reduce the inflammation and hyperexcitability that is normally exhibited as glucose metabolism declines in the brain.18, 19
Zhou Nutrition’s MCT Powder is another great quality MCT powder to try out. Taking a note from Perfect Keto, Zhou uses only Acacia Fiber during its manufacturing process and avoids all use of the common additives and fillers you see in most MCT powders. Zhou’s MCT Powder is made with the patented “goMCT” MCTs. While you don’t get the delicious flavors Perfect Keto have perfected, Zhou’s MCT Powder is a proven product pushing a 4 digit tally in positive reviews. Hundreds have attested to its true lack of flavor and positive ketone results.
Another factor to consider is that in nutritional ketosis the liver makes a steady supply of ketones and continuously releases them into the circulation. In contrast, most ketone supplement protocols involve bolus intakes that don’t mimic the endogenous release pattern. The extent to which this impacts metabolic and signaling responses across different tissues remains unclear.
Hi, I still a little confused about when or how to take this. I am trying to get adapted and minimize the flu. Is it most beneficial before eating, after eating, with food or in place of food? I have been keto in the past but this time I am not switching over to fat burning mode even though my macros are good. ( I am thinking it is just too many calories and carbs at this point but I get hungry!) Help please.
When your body transitions from using energy from carbohydrates to ketones, there can be a lot of nasty and unwanted side effects. These include low energy, bloating, irritability, headaches and fatigue. This is because your body is “in between” burning carbs and burning ketones and hasn’t become efficient at burning ketones and producing them from your fat stores yet.
KE was synthesized as previously described . BMS is a novel agent (sodium/potassium- βHB mineral salt) supplied as a 50 % solution containing approximately 375 mg/g of pure βHB and 125 mg/g of sodium/potassium. Both KE and BMS were developed and synthesized in collaboration with Savind Inc. Pharmaceutical grade MCT oil (~65 % caprylic triglyceride; 45 % capric triglyceride) was purchased from Now Foods (Bloomingdale, IL). BMS was formulated in a 1:1 ratio with MCT at the University of South Florida (USF), yielding a final mixture of 25 % water, 25 % pure βHB mineral salt and 50 % MCT. BD was purchased from Sigma-Aldrich (Prod # B84785, Milwaukee, WI).
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).
To be in ketosis, you need to get very specific about the macronutrient ratios hanging off your fork. This means eating 75% fats, 20% protein and 5% carbohydrates. It’ll see you getting 5-10% of your total calories from carbohydrates, which is roughly 25-30g of carbs per day, and diligently keeping this below the 50g threshold creates the ketosis that burns stored fat. Unlike the no-limit-protein option on the table when going low carb, eating more than 0.67-0.81g of protein per pound of bodyweight can hoof you out of ketosis because too much of it can be converted into glucose, blunting the benefits of the ketones. On the plus side, you will have a high fat intake, making your energy levels more balanced so you can train at higher intensities.
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.
The body will start making ketones when either we go extended periods without food, or we restrict the one dietary component that stops ketone formation – this being carbohydrates and also minimising protein intake as this also can halt ketone. In turn, your primary source of food is fat, with very little carbohydrate and a small amount of protein.”
If you have tried other ketone supplements that haven’t worked as promised or tasted terrible. Have no fear. This stuff is what a ketone supplement should be. It’s incredible what customers tell me. How it’s given them more energy, focus, drive. Helped them lose weight and suppress their appetite. Help them train harder at the gym and all kinds of great stories.*
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.
This fasting process will not only activate autophagy in your cells, it will also increase your ketones much more quickly than if you were just eating a standard ketogenic diet. If you start implementing intermittent fasting and activities (like walking, cycling, or lifting weights) together, you can raise ketone levels and increase autophagy more than you would with intermittent fasting alone. This suggests that intermittent fasting would be a great addition to your life, but it is important to be familiar with the negative symptoms that can arise before you start.
Do you need carbs to train? No. Again this is an anecdote only, but I have done numerous training sessions in a carb deprived state. Heck some of my best training sessions where done in a fasted, carb deprived state. And there are a lot of endurance athletes who are using a ultra-low carb/ketogenic diet and putting up some great times (more on this below).
Ketone Esters: Synthetically-made compounds that link an alcohol to a ketone body, which is metabolised in the liver to a ketone. Ketone esters are used primarily in research for testing their efficacy in elevating ketone body levels (below is a generic structure of a BHB ester). Yet, the first commercial Ketone ester drink will be available in 2018 by HVMN. Research esters are reportedly very unpleasant tasting which HVMN hopes to change.
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.
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).
Other studies have found that fasting was as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of chemotherapeutic drugs against melanoma, glioma, and breast cancer cells. Although this research may not apply to your life, it does suggest that intermittent fasting can help support your body in times of toxic stress.
Blood glucose concentrations are decreased during both exogenous and endogenous ketosis, although by different mechanisms. During endogenous ketosis, dietary carbohydrate deficit is the underlying cause of low blood glucose, along with reduced hepatic gluconeogenesis and increased ketone production (Cahill et al., 1966). With exogenous ketosis, carbohydrate stores are plentiful, yet ketones appear to lower blood glucose through limiting hepatic gluconeogenesis and increasing peripheral glucose uptake (Mikkelsen et al., 2015). One clinical use of the ketogenic diet is to improve blood glucose control, yet the elevated blood FFA may increase the risk of heart failure (Holloway et al., 2009). Thus, the ability of exogenous ketones to lower blood glucose without elevating blood FFA concentrations could deliver the desired effect of the diet, whilst also decreasing a potential risk.
Ketone supplements contain exogenous ketones—synthetic ketones made in a lab. Most use a type of ketone called beta-hydroxybutyrate (BHB), which is the same as the ketones the body produces naturally. “We’re literally biohacking," says Amie Heverly, who began taking a ketone supplement called Prüvit last year and now works as a promoter selling Prüvit products. "You’re not adding a foreign substance to your body, because BHB is identical to what your body would naturally produce,” she explains.
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)
The keto-esters are more appropriate for delivering higher doses of BOHB, but with repeated dosing can push the limits of taste and GI tolerance. There has been fairly extensive research on a compound 3-hydroxybutyl 3-hydroxybutyrate that is converted via hydrolysis and liver metabolism to yield 2 molecules of ketones, presumably mostly D-BOHB (Clarke 2012 and 2014). In a study involving lean athletes, an approximate 50 gram dose raised blood BOHB levels to 3 mM after 10 min and reached 6 mM by 20 min. Submaximal exercise resulted in increased ketone disposal from 2 to 3 hours and contributed significantly to whole body energy use during exercise (Cox 2016). This product has been shown to significantly reduce appetite after a single dose (Stubbs 2018) but its effect on body weight in humans over a longer period of time has not been studied, nor has its effect on blood glucose control been reported in humans with type 2 diabetes. However a single dose prior to a glucose tolerance test in healthy humans reduced blood glucose area-under-curve by 11% and non-esterified fatty acid area-under-curve by 44% (Myette-Cote 2018).
The problem? Exogenous ketone supplements work by flooding your bloodstream with ketones. But unless you’re also eating a ketogenic diet (and producing a steady stream of ketones naturally), those supplemental ketones won’t stick around forever. “The benefit of exogenous ketones is limited due to their excretion through the urine,” explains Madge Barnes, MD, family medicine specialist with Texas Health Family Care. In other words? They’ll only work for a few hours until you pee them out. As a result, you need to keep on supplementing—which can get expensive. Twenty single-serving packets of Prüvit’s Keto//OS MAX Pure Therapeutic Ketones, for example, cost $130. (The company doesn’t specify how often you should take them.)
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.
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.
Exogenous ketones are powerful. They will get you into ketosis whether keto-adapted or not. The benefits of this range from weight loss to sustained mental and physical energy. The benefits are the same as those from nutritional ketosis, however, they’re not a substitute for nutritional ketosis. More on that below before we get into the top 5 exogenous ketones for 2018.
Recently, a friend of mine’s dad had high blood pressure. His doctor told him to stop consuming eggs and to avoid adding extra salt to his foods. That’s it. His recommendation was to rid a good, high-quality protein source, yet French fries, chicken nuggets, and even chicken noodle soup were all presumably okay. I’ll never understand some of these recommendations; nonetheless, they happen day in and day out, all over the world.
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.
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.
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.
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.
Zenwise, you should consider offering this through an email subscriber list to gain **more** loyal (& repeat) customers by offering them better prices. We all know it's cheaper to find ways to keep customers than to go out and find new ones (about 5x cheaper in fact!), plus my guess is Amazon is getting 30% margin AT LEAST). If I saw that you offered a 25% discount when buying directly, I'd keep using the product.
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