Hi Mark, sorry this is off topic but not sure where to send a question for a future Ask Mark. I’m about to go into my yearly physical and I am wondering if there is any specific bloodwork that you like to do for your annual check up. I’m 47 year’s old and the than the basic blood work like lipid panel, etc..I’m going to ask my doctor to test my testosterone, HbA1C, fasting insulin, and Vitamin D levels. I’m also going to ask my doctor to do a stool test to check for parasites or other infections I may have picked up from open water swimming for triathlons. Can you recommend any other blood work that might be useful? Thanks!

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).
Blood d-βHB concentrations rapidly increased to a maximum of 2.8 ± 0.2 mM following the KE drink and to 1.0 ± 0.1 mM following the KS drink (Figure ​(Figure1A).1A). After the peak was reached, blood d-βHB disappearance was non-linear, and followed first order elimination kinetics as reported previously (Clarke et al., 2012b; Shivva et al., 2016). d-βHB Tmax was ~2-fold longer following KS drinks vs. KE drinks (p < 0.01, Figure ​Figure1B),1B), and KS d-βHB AUC was ~30–60% lower than the KE drink (p < 0.01, Figure ​Figure1C1C).
That’s not all. Though Prüvit in particular has a legion of fans (the brand has nearly 35,000 Instagram followers and some 256,000 likes on Facebook) and a small team of affiliated medical experts, there’s no hard science on Prüvit or similar products. (Prevention reached out to several Prüvit experts and employees for interviews but did not receive a response.) The research page on the brand’s website does include links to legit scientific studies. But the studies are on the keto diet—not on Prüvit’s products. When it comes to research on the actual supplements, the brand’s website simply says “Human studies on finished products (underway) at various universities and research facilities.” In other words, there’s no scientific evidence available yet to show that they actually work.
This is another point that Brianna Stubbs put me onto: often, ketone-salt companies use terms such as “technology developed by Dominic D’Agostino” as a tool to market their products. Dom D’Agostino holds the patent for the technology being used but is not associated with the products and does not necessarily promote them. In many cases, this feels like a marketing strategy that name-drops a famous keto expert in order to make a product sound more legitimate. There is an example of this on Real Ketones’ website.
The difference in peak blood d-βHB concentrations between matched amounts of βHB as ester or salts arose because the salt contained l-βHB, as the blood concentrations of d- plus l-βHB isoforms were similar for both compounds. It is unclear if kinetic parameters of KE and KS drinks would be similar if matched d-βHB were taken in the drinks. Unlike d-βHB, blood l-βHB remained elevated for at least 8 h following the drink, suggesting an overall lower rate of metabolism of l-βHB as urinary elimination of l-βHB was in proportion to plasma concentration. Despite similar concentrations of total βHB, breath acetone was ~50% lower following KS drinks compared to KE, suggesting fundamental differences in the metabolic fates of D- and L-βHB. These findings support both previous hypotheses (Veech and King, 2016) and experimental work in rats (Webber and Edmond, 1977), which suggested that the l-isoform was less readily oxidized than the d-isoform, and is processed via different pathways, perhaps in different cellular compartments. It seems that l-βHB is not a major oxidative fuel at rest, and may accumulate with repeated KS drinks. However, the putative signaling role of l-βHB in humans remains unclear. In rodent cardiomyocytes, l-βHB acts as a signal that modulates the metabolism of d-βHB and glucose, Tsai et al. (2006) although no differences in blood glucose were seen here. Furthermore, L-βHB can act as a cellular antioxidant, although to a lesser extent than D-βHB (Haces et al., 2008).
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.
All data are presented as the mean ± standard deviation (SD). Data analysis was performed using GraphPad PRISM™ version 6.0a and IBM SPSS Statistics 22.0. Results were considered significant when p < 0.05. Triglyceride and lipoprotein profile data were analyzed using One-Way ANOVA. Blood ketone and blood glucose were compared to control at the applicable time points using a Two-Way ANOVA. Correlation between blood βHB and glucose levels in ketone supplemented rats was compared to controls using ANCOVA analysis. Organ and body weights were analyzed using One-Way ANOVA. Basal blood ketone and blood glucose levels were analyzed using Two-Way ANOVA. All mean comparisons were carried out using Tukey’s multiple comparisons post-hoc test.
An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017), in three extremely ill pediatric patients (Plecko et al., 2002; Van Hove et al., 2003; Valayannopoulos et al., 2011) and in cyclists (O'Malley et al., 2017; Rodger et al., 2017). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis. Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, d-βHB, and l-βHB, despite the metabolism of l-βHB being poorly understood (Webber and Edmond, 1977; Scofield et al., 1982; Lincoln et al., 1987; Desrochers et al., 1992). The pharmacokinetics and pharmacodynamics of KS ingestion in healthy humans at rest have not been reported.
If the goal is to deplete glucose levels so that we can start producing ketone bodies, then forcibly exerting physical energy through exercise is a great way to go about it. Keeping it relatively low intensity to begin with and working out in the morning is recommended as this helps to keep down your cortisol (stress hormone) levels. This only applies at the beginning of your keto adaptation process, as intense workouts such as HIIT once already keto-adapted will be completely fine.
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.
Working memory involves temporarily storing and manipulating information. The game involves seeing three cards – a top card with a symbol that then moves along a track and is flipped over, exposing a new card above. The goal is to remember the symbol of the cards two cards back and indicate whether it matches the visible card or not. If you have ever played dual n-back games, this is very similar.
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, and women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is really important to know what combination of compounds you are consuming, particularly while you are on this very strict diet because the wrong balance can really mess with you in the long term and won't give you the high performance that you are looking for. 

Our bodies are produce three types of ketone bodies for fuel: beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. Each is used by the body differently. Acetone is the least abundant, produced in much smaller amounts, and is usually exhaled through the lungs rather than being used as fuel.3 Acetoacetate is part of the metabolic pathway whereby humans make and use ketones, but it tends to be found in the blood at lower levels than BHB.

A small side effect for some people is “ketosis breath”. Many people on a ketogenic diet have experienced this temporary phenomenon, and those taking exogenous ketones can experience it as well. The smell of your breath when you are early in the ketogenic diet can have a hint of acetone to it, and it might be mildly unpleasant, but it’s also harmless. Most gum is pretty low in carbohydrates and is a great option while your keto breath fades.
Possible GI distress (flatulence) at exceptionally high doses –  In the studies referenced in this article, exogenous ketones taken in large doses occasionally resulted in GI distress, especially flatulence. However, the cause of this is hypothesized to be due to the fact that ketones were mixed in a milky fluid that wasn’t very palatable. If you’re taking a nominal dose of exogenous ketones the likelihood of GI distress is rather low. Moreover, if some GI distress is prevalent, it should improve as you become accustomed to taking ketones.

The reason for testing after one hour was based on Prüvit’s “59-minute test”, which recommends testing ketones 45-60 minutes after taking the supplement (by the way, saying “59 minutes” instead of 60 minutes or 1 hour just sounds like another marketing gimmick to me). Kegenix Prime also promises “ketosis in 60 minutes” on its packaging. We carried out the testing at more or less the same time each day.

Will taking exogenous slow down my fat loss? Since now before digging into my body for energy/ketones, I will first use up the exogenous ketones I ingest. Also do exogenous ketones somehow help get even more keto adapted, keeping in mind I have been on a strict keto diet without a problem and don’t mind it at all. Outside of performance improvements, do you think exogenous ketones is for someone like me who is primarily looking for fat loss.
Hi! I have what might be a silly question about using these supplements. What happens if you are taking them and your diet goes off the rails, like you take the Keto//OS and then eat a bunch of pizza or chocolate. Does your body just immediately revert back to using the carbs for energy instead of the ketones? Or, if it doesn’t, would that mean your body would just store those carbs as fat? I realize that ideally you wouldn’t eat the pizza, but sometimes I do and I worry about what exactly I’m doing to my body if I’ve also taken ketones.
Lastly, EK products in general ​are usually in the form of salts, which is why they are referred to as BHB Salts. The BHB ketones are bound to common salts such as sodium​, calcium, magnesium and potassium​ to improve absorption rate. These salts are also the core electrolytes your body needs to help you avoid feeling mentally drained and physically lousy during the keto-flu transition period.

A sound sleep is highly associated with the dark. Also, studies have proven that our body’s natural defense mechanisms against cancer cells get activated in the absence of light (that’s why sleeping is the best way to natural healing). So turn off all the lights, TV screen, lamps, and all other light emitting devices at least 30 minutes before going to sleep. With this trick, you are actually preparing yourself to fall asleep.

Exogenous ketones provide the body with another fuel to employ. Think about it like an electric car that runs on both gas and electricity: by consuming ketones along with carbohydrates, the body will preferentially burn the ketones first, saving the carbohydrates for later. Exogenous ketones allow us to enter a metabolic state that wouldn't occur naturally: the state of having full carbohydrate stores, as well as elevated ketones in the blood. This could be advantageous to athletes looking to boost their physical performance. 
Once you hit the bed, the adrenal glands will be off and the body will enter the anabolic stage. This will allow your body to repair itself. If you stay up late for long periods of time your body will enter the hypercatabolic state. In this state, the levels of cortisol in your body increase significantly. This also increases the insulin resistance of the body which would again increase the blood sugar levels.
Also, it’s important to remember that just because something may be SAFE (and to reiterate, I’m not saying a long term ketogenic diet is safe), it doesn’t mean it’s good for you or beneficial. Running Marathons could be considered safe (especially if it’s on a closed race circuit), but does this mean it’s good for you? Or should you be out running marathons every day?
An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017), in three extremely ill pediatric patients (Plecko et al., 2002; Van Hove et al., 2003; Valayannopoulos et al., 2011) and in cyclists (O'Malley et al., 2017; Rodger et al., 2017). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis. Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, d-βHB, and l-βHB, despite the metabolism of l-βHB being poorly understood (Webber and Edmond, 1977; Scofield et al., 1982; Lincoln et al., 1987; Desrochers et al., 1992). The pharmacokinetics and pharmacodynamics of KS ingestion in healthy humans at rest have not been reported.
When your body is done using up a certain substrate to create energy (acetyl-CoA) after eating carbohydrates, it will start to find creative ways to get the job done. This is something that you want to happen. This is the switch to ketosis. If you didn’t do this, you’d be dead after fasting for a very short period of time. Under normal circumstances, the liver will start making beta-hydroxybutyrate from long chain and medium chain fatty acids that are liberated from your fat tissue. You are turning fat into fuel. Good work. This is why people can fast for months at a time and still function like normal humans.
The “BHB salt” is simply a compound that consists of sodium (Na+), potassium (K+), and the ketone body β-hydroxybutyrate. In supplements like Pruvit’s Keto OS these individual components are being held together by ionic bonds; however, when you consume the product, it is absorbed into the blood where it dissociates into free Na+, K+, and BHB since it is a water-based solution. Thus, consuming the product directly and immediately puts more ketones into your blood.
I’m just getting back into an active lifestyle after being sedentary for a few years.. Rough start I must admit but I’m focused.. Objective is to lose 80lbs. I’ve previously had my body in ketosis when I was dieting and working out so I can attest to the benefits I’ve felt before.. Now that I see Exogenous Ketones are available, I’m wondering if it’s recommended to start taking them to help jumpstart my body into ketosis since that is the goal for burning fat…

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
With single doses of the D-BHB ester as a sports drink, gastrointestinal (GI) side effects are rare. Some studies have reported mild GI side-effects of HVMN Ketone drinks at extremely high doses (4x serving size) or when given in a thick, meal replacement formulation.10,13 However, other studies of athletes reported there were no side-effects of ketone ester drinks hindering sport performance.11,14
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
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”).
Over five visits, participants (n = 16) consumed either 4.4 mmol.kg−1 of βHB (2.2 mmol.kg−1 or 395 mg/kg of KE; 1 mole of KE delivered 2 moles of d-βHB equivalents): twice whilst fasted, and twice following a standardized meal, or an isocaloric dextrose drink without a meal. To improve palatability, drinks were diluted to 500 ml with a commercially available, citrus flavored drink containing 65 kCal (5 g of carbohydrate) (Glaceau, UK). The dextrose drink was taste-matched using a bitterness additive (Symrise, Holzminden, Germany). The standard meal consisted of porridge oats (54 g), semi-skimmed milk (360 ml) and banana (120 g), giving 600 kCal per person, with a macronutrient ratio of Carbohydrate: Protein: Fat of 2:1:1.
When you restrict carbs, the kidneys excrete a lot of sodium. Not replacing this sodium can leave you feeling light headed. I recommend having a big glass of spring water with ½ teaspoon of Celtic sea salt twice a day (first thing in the morning and midafternoon are two times that work well). A long with this, make sure you use a lot of salt on your meals.

Many of us have heard the saying, “Don’t blame the butter for what the bread did.”  Similarly, don’t blame the sodium for what the fries did.  Sodium has been shown to help maintain fluid balance, normal muscle and nerve function, and blood pressure and volume[1]. The movement of sodium ions and other electrolytes across cell membranes helps to facilitate muscle contraction and nerve impulses. Electrolytes also help to maintain fluid balance across intracellular and extracellular spaces and blood volume.
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.
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).
That’s not to say that the supplements don’t work. They very well might. But they could also be useless—or even dangerous, says Christine Palumbo, RDN, Nominating Committee member for the Academy of Nutrition and Dietetics. As of right now, there’s no way to know. “Currently, there’s just not enough evidence from research studies to answer those questions,” Barnes adds.
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.

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