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

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).
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)

Recent studies suggest that many of the benefits of the KD are due to the effects of ketone body metabolism. Interestingly, in studies on T2D patients, improved glycemic control, improved lipid markers, and retraction of insulin and other medications occurred before weight loss became significant. Both βHB and AcAc have been shown to decrease mitochondrial reactive oxygen species (ROS) production [36–39]. Veech et al. have summarized the potential therapeutic uses for ketone bodies [28, 40]. They have demonstrated that exogenous ketones favorably alter mitochondrial bioenergetics to reduce the mitochondrial NAD couple, oxidize the co-enzyme Q, and increase the ΔG’ (free enthalpy) of ATP hydrolysis [41]. Ketone bodies have been shown to increase the hydraulic efficiency of the heart by 28 %, simultaneously decreasing oxygen consumption while increasing ATP production [42]. Thus, elevated ketone bodies increase metabolic efficiency and as a consequence, reduce superoxide production and increase reduced glutathione [28]. Sullivan et al. demonstrated that mice fed a KD for 10–12 days showed increased hippocampal uncoupling proteins, indicative of decreased mitochondrial-produced ROS [43]. Bough et al. showed an increase of mitochondrial biogenesis in rats maintained on a KD for 4–6 weeks [44, 45]. Recently, Shimazu et al. reported that βHB is an exogenous and specific inhibitor of class I histone deacetylases (HDACs), which confers protection against oxidative stress [38]. Ketone bodies have also been shown to suppress inflammation by decreasing the inflammatory markers TNF-a, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46, 47]. Therefore, it is thought that ketone bodies themselves confer many of the benefits associated with the KD.

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.
A common question is why BHB is the go-to ketone body for exogenous ketone supplements. The likely reason is a combination of its efficient conversion into energy and its ease of formulation. In other words, that it is easier to formulate BHB into a nutritional supplement. And the body efficiently converts BHB to acetoacetic acid, which effectively raises blood ketone levels.
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.)
I don’t recommend that you go straight for a 1-2 day fast, but begin by restricting yourself to certain eating windows. Typically people restrict themselves to the hours of 5pm – 11pm. People often refer to their fasting windows by numbers: 19/5 or 21/3, for example, means 19 hours of fasting and 5 hours eating or 21 hours fasting and 3 hours eating, respectively.
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.

Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.
The famous keto-breath is powerful enough to throw shade on your increasingly ripped rig. The mouth-based ketones are released when your body scalds fat are responsible for the pong. Going into ketosis by changing your diet means your body doesn’t have carbs as a fuel source, so you’re using fats and proteins for energy, which fuels the potency of the fireworks seeping from your grill. The same can happen when taking supplements, but not by the same degree – proving that changing your diet it obviously a more potent fat burning tool. A lot of people also report gastric distress, so you could offend those you’re co-habituating with. What’s more, they can have a slight diuretic effect, which can deplete your magnesium, potassium and sodium stores, so make sure your levels are topped up when you’re out for a extra long exercise stint. Research in Nutrition and Metabolism on animals, found there were no negative side effects, but whether this extends to humans is still up for discussion. Fortunately, you’re more likely benefit from the upsides such as improved endurance, appetite suppression and fat burning.
How BHB turns into energy is a fairly simple process. As we’ve mentioned, beta hydroxybutryate eventually leads to energy production after you consume it or after your body breaks stored body fat down. It does this by going into the cell, entering the mitochondria (energy factories) at which stage it cleaves the carboxyl acid group and becomes acetoacetate (another “ketone body”). Acetoacetate turns into acetoacetyl-CoA, which then is cleaved to acetone (another “ketone body”) and acetyl-CoA. Acetyl-CoA is the whole reason we want BHB in the first place. This jumps into what is called the Kreb’s cycle (don’t you remember any of your biochemistry classes?) and is churned into ATP — the energy currency of your cells!
Ketoacidosis is driven by a lack of insulin in the body.  Without insulin, blood sugar rises to high levels and stored fat streams from fat cells.  This excess amount of fat metabolism results in the production of abnormal quantities of ketones. The combination of high blood sugar and high ketone levels can upset the normal acid/base balance in the blood and become dangerous.  In order to reach a state of ketoacidosis, insulin levels must be so low that the regulation of blood sugar and fatty acid flow is impaired.
Although decreases in FFA, TG and glucose occurred, there were no significant differences between the KE and KS drinks or with intake amount. Ingestion of ketone drinks significantly decreased overall mean plasma FFA from 0.7 to 0.4 mM, TG from 1.1 to 0.9 mM and glucose from 5.7 to 4.8 mM after 1 h (all p < 0.05). Concentrations were the same as at baseline by 4 h, with FFA at 0.6 mM, TG at 0.9 mM and glucose 5.1 mM (Figures 2A–C). There was a rise in insulin concentrations 30 min following all drinks, probably due to the small amount of carbohydrate in the sweetener (Figure ​(Figure2D2D).
Athletic performance benefits: The use of exogenous ketone supplements for bettering physical/athletic performance is promising for several reasons. Firstly, taking exogenous ketones (particularly BHB salts) induces acute nutritional ketosis for upwards of eight hours, mimicking fasting physiology (e.g. increases fat burning, insulin sensitivity, etc.).[3]
Glucose and BHB went down slightly throughout the effort and RQ fell, implying a high rate of fat oxidation. We can calculate fat oxidation from these data. Energy expenditure (EE), in kcal/min, can be derived from the VO2 and VCO2 data and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ gives us a good representation of how much of the energy used during the exercise bout was derived from FFA vs. glucose—in this case about 87% FFA and 13% glucose. So fat oxidation was approximately 12.7 kcal/min or 1.41 g/min. It’s worth pointing out that “traditional” sports physiology preaches that fat oxidation peaks in a well-trained athlete at about 1 g/min. Clearly this is context limited (i.e., only true, if true at all, in athletes on high carb diets with high RQ). I’ve done several tests on myself to see how high I could push fat oxidation rate. So far my max is about 1.6 g/min. This suggests to me that very elite athletes (which I am not) who are highly fat adapted could approach 2 g/min of fat oxidation. Jeff Volek has done testing on elites and by personal communication he has recorded levels at 1.81 g/min. A very close friend of mine is contemplating a run at the 24 hour world record (cycling). I think it’s likely we’ll be able to get him to 2 g/min of fat oxidation on the correct diet.

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