Another source of the D-BOHB isomer is an evolutionarily ancient energy source for micro-organisms. Poly-BOHB is a long chain of D-BOHB molecules strung end-to-end. It functions in many single-cell organisms as a concentrated energy source similar to glycogen in mammals, but whereas glycogen breakdown releases individual glucose molecules, poly-BOHB hydrolysis releases single D-BOHB molecules.
I’m often asked if it’s necessary to buy and use keto products like urine sticks. They’re small test strips that you dip in urine to see if your body is producing ketones (and therefore indicate if you’ve entered ketosis.) There's very little information on how to know that you are in ketosis other than using these ketones supplements because they are as accurate as can be in determining your current state. Outside of that, you can only guess if you are in it or not by your body's performance.
Beta hydroxybutyrate floats around in your blood, and importantly, can cross different barriers to be able to be turned into energy at all times. One of the most important areas where this happens is in the brain. The blood-brain barrier (BBB) is usually a very tightly regulated interface that doesn’t allow the transfer of many molecules, but since BHB is such a rock star and so hydrophilic, your brain knows to let it in so it can bring energy to the party at any time. This is one of the main reasons why increased levels of ketosis lead to improved mental clarity, focus and reduction in neurodegenerative diseases.

In the second of these posts I discuss the Delta G implications of the body using ketones (specifically, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP generation, instead of glucose and free fatty acid (FFA). At the time I wrote that post I was particularly (read: personally) interested in the Delta G arbitrage. Stated simply, per unit of carbon, utilization of BHB offers more ATP for the same amount of oxygen consumption (as corollary, generation of the same amount of ATP requires less oxygen consumption, when compared to glucose or FFA).


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.
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.

The CNS cannot use fat as an energy source; hence, it normally utilizes glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources, and as demonstrated by the classic experiments of Cahill and colleagues4 this alternative energy source is derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies (KBs), that is, acetoacetate, β-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs principally in the mitochondrial matrix in the liver.6


We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
The CNS cannot use fat as an energy source; hence, it normally utilizes glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources, and as demonstrated by the classic experiments of Cahill and colleagues4 this alternative energy source is derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies (KBs), that is, acetoacetate, β-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs principally in the mitochondrial matrix in the liver.6
The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat [27]. 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 [35].
Ketones are also a cleaner-burning fuel than carbs. They’re burned for energy in the mitochondria, and fewer free radicals (a highly-reactive, short-lived uncharged molecule) are generated when compared to burning glucose.15 What’s more, ketone molecules themselves cause a decrease in production of free radicals,21,22 while also increasing glutathione–a powerful antioxidant protecting against mitochondrial damage induced by free radicals.23
You must realise that our bodies are lazy and switching to a new energy source means hard work, that means that your body will not do this easily and you basically have to force it. One way to speed up this process is to put your body into fight or flight mode. My preferred  controlled exercise to do this is to have a high intensity workout followed immediately by a  cold shower.  I am describing it in the article to go slowly, but in this case it will actually be beneficial if you can force your self to go straight into a cold shower and try to stay there at least 2 minutes. One of the benefits of this that your body will produce the hormone noradrenaline. Obviously this is something for people in perfect health. Please advice your doctor before you want to take cold showers.
The metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated FFA concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis. Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.

Response inhibition is the ability to suppress inappropriate responses that interfere with goal-directed actions. Two cards are shown, one above the other, each containing the name of a color in a certain color. The goal is to rapidly indicate if the meaning of the color on top (i.e. “yellow”) matches the color of the color on the bottom (i.e., card says “red” but is colored yellow).

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.
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.
The benefits of intermittent fasting translate to untrained overweight and obese individuals as well. One study published in Obesity Reviews found that eating fewer calories is effective for fat loss, but it does come with some muscle loss. However, if the subjects fasted for 24 hours and ate as much as they wanted on the next day for a period of 12 weeks, they lost significantly less muscle mass.

Your body uses the energy source that is the easiest to use, in our case this is glucose. Glucose is just a type of sugar. As our body cannot store glucose as such it stores the extra glucose in form of glycogen that is stored in our liver and muscles. To initiate production of ketones in your body as fast as possible you must deplete your body of glycogen reserves. The best way to do this is a simple 24 hours fast. This will deplete your glycogen stores as fast as possible. If you don’t over eat for dinner or you even skip it all together you will already wake up in state of mild ketosis the next morning due to the overnight fast. Here are also described some signs that you are in Ketosis already.
Price: The supplements are expensive – very expensive. At the top end, if you follow Prüvit’s guidelines on “getting in the n8tive zone” (which is such a gimmicky marketing slogan it almost makes me cringe), you will require 2 servings of their Keto-OS product per day. This means around 60 servings per month, which will set you back a whopping $390 per month if you buy direct from their website! In the case of Prüvit, this is in part due to the multi-level marketing structure they operate under.

I have, though, recently been diagnosed with ovarian cancer. After reading through your blog, I noticed there was a little about Ketogenetic diet and cancer. I purchased the MCT oil powder in hopes that will help me get into ketosis for the purpose of “starving” the cancer cells. Other then focus, I didn’t see any particular format for something like this. Here are my questions: How much of the powder should I take? And do you think the diet plus the MCT oil is a good idea for 1) aiding chemotherapy and 2) helping shrink the number of cancer cells?
Studies show that exercising depletes both liver and muscle glycogen faster than fasting [4]. For example, swimming for an hour and a half depletes the same amount of glycogen as a 24-hour fast. However, it's a good idea to eat a tiny amount of carbs and protein before and after a workout to prevent muscle damage. Your body can break down proteins in your muscles if glycogen stores get depleted during workouts.
It’s not clear that the Weir coefficients used to estimate EE are relevant for someone in ketosis, let alone someone ingesting exogenous BHB. (The Weir formula states that EE is approximated by 3.94 * VO2 + 1.11 * VCO2, where VO2 and VCO2 are measured in L/min; 3.94 and 1.11 are the Weir coefficients, and they are derived by tabulating the stoichiometry of lipid synthesis and oxidation of fat and glucose and calculating the amount of oxygen consumed and carbon dioxide generated.) While this doesn’t impact the main observation—less oxygen was consumed with higher ketones—it does impact the estimation of EE and substrate use.

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