Participants consumed 13.2 mmol.kg−1 of βHB (6.6 mmol.kg−1 or 1,161 mg/kg of KE) over 9 h, either as 3 drinks of 4.4 mmol.kg−1 of βHB at 3 h intervals (n = 12), or as an initial bolus of 4.4 mmol.kg−1 of βHB given through a nasogastric tube, followed by an infusion of 1.1 mmol.kg.h−1, beginning 60 min after the initial bolus, for 8 h (n = 4). Two participants completed both conditions (total n = 14). In both conditions, the KE was diluted to 1.5 L using the same citrus water as used in Study 2.
North Americans typically live pro-inflammatory, pro-disease lives (think about your everyday: likely sitting in a flexed position for hours on end, not enough natural sunlight, not enough movement, artificial food stuffs, artificial colouring, going to bed late, blue light exposure, less in-person contact with our loved ones, late night snacks, the list goes on and on).
The ketogenic journey should be more of a lifestyle than one that acts like a fad. So taking more than a day for your body to enter ketosis should not be the greatest of concern. It’s more important to stay discipline and to consistently keep your body in a fat-burning state. Although, if you are someone who has fallen out of ketosis after a cheat day, or rather somebody who is just starting out and finding it longer than expected to enter ketosis, then this article can definitely help in that respect. It’s nothing new, and it’s definitely no secret but strict dieting, fasting, exercise, controlling stress levels, sleep, and certain supplements can help you boost ketogenesis!
Once the body is able to generate energy with the help of exogenous ketones which are present in the bloodstream, it would start looking for other sources of ketones. This would encourage the body to tap into the vast reserve of fat which is accumulated in the body. Thus, the process of ketosis is accelerated when you consume extra exogenous ketones. This also leads to quicker weight loss and the body entering ketosis faster.
I came across a new company called KetoneAid that has begun producing small batches of ketone monoesters (KMEs). The main molecule in their product (D-β-hydroxybutyrate / D 1,3-butanediol) is based on a five-year, $10M study commissioned by the Defense Advanced Research Projects Agency (DARPA), looking to create the most powerful source of energy for special operations soldiers such as Navy SEALs, when undertaking very physically and cognitively challenging missions. In fact, the main researcher of the DARPA study is Dr. Richard Veech, the same person that authored the longevity study I just mentioned. Very cool.
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.
Most people know that you can lose weight by consuming fewer carbs and a lot more protein. However, it's very important that you watch your protein intake carefully if you want to achieve ketosis quickly. There needs to be a balance in the amount of protein you are consuming, since too much of it is not going to be beneficial for you. What you need to remember is that this process is all about getting the right balance of fats, proteins, magnesium, salts, etc., to get your body into ketosis faster.
Another important difference between endogenous and exogenous BOHB is that most synthetic BOHB used in dietary supplements is a mixture of the two ‘D’ and ‘L’ isomers, whereas endogenously produced BOHB consists of just the D-isomer. Metabolically, the two isomers are very different, and current published information indicates that most of the energy and signaling benefits of BOHB derive from the D-form. This is potentially problematic because the L-isomers are not metabolized via the same chemical pathways as the D-forms (Lincoln 1987, Stubbs 2017), and it remains unclear whether humans can convert the L-form to the D-form.
We carried out the testing across five different days, leaving at least two days between the different testing days so that my teammates had time to recover from the physical performance test each time. The reason we needed five days was that we included a placebo (an artificially flavored drink with no caffeine content) alongside the four brands we tested. Our teammates didn’t know that one of the supplements was a placebo. We also gave everyone a different supplement each time, to rule out any improvement in the tests being a result of people simply getting better at those tests over time.
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!
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.
Serial drinks or a continuous NG infusion of KE effectively kept blood ketone concentrations >1 mM for 9 h (Figure (Figure6).6). With drinks every 3 h, blood d-βHB rose and then fell, but had not returned to baseline (~ 0.1 mM) when the next drink was consumed. There was no significant difference in d-βHB Cmax between drinks 2 and 3 (3.4 ± 0.2 mM vs. 3.8 ± 0.2 mM p = 0.3), as the rate of d-βHB appearance fell slightly with successive drinks (0.07 ± 0.01 mmol.min−1 and 0.06 ± 0.01 mmol.min−1 p = 0.6). d-βHB elimination was the same after each bolus (142 ± 37 mmol.min, 127 ± 45 mmol.min; and 122 ± 54 mmol.min). When KE was given via a nasogastric tube, the initial bolus raised blood d-βHB to 2.9 ± 0.5 mM after 1 h, thereafter continuous infusion maintained blood d-βHB between 2–3 mM. Total d-βHB appearance in the blood was identical for both methods of administration (Serial drinks AUC: 1,394 ± 64 mmol.min; NG infusion AUC: 1,305 ± 143 mmol.min. p = 0.6).
While the KetoneAid folks have been seeing tremendous success working with elite athletes to improve athletic performance, I thought it would be interesting to quantify the effects of ketone esters on cognitive performance. For the week prior to taking the ketones, I re-established baseline scores in a number of cognitive testing areas using Lumosity*:
Calories do matter, even on a ketogenic diet. If you consume more calories than your body uses, you’re going to gain weight. Period. What you mean to say is that it’s very difficult to eat your entire day’s worth of calories on a ketogenic diet because fats are so satiating. This distinction is important to keep in mind for those who generally have a voracious appetite (like me).
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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...
In addition, the body regulates ketone production via ketonuria (peeing out excess ketones) and ketone-induced insulin release, which shuts off hepatic ketogenesis (the liver making more ketones when you have enough). The insulin from this process could be increasing glucose disposal which, when coupled with PDH activation, could drive glucose levels quite low.
EK use can be compared to the nootropics that have been developed for optimizing focus, memory creation, and faster cognitive performance. While you may not notice this effect on a minute to minute basis if you keep a journal of “forgetful moments” you’ll find that you have fewer of them as time goes on. You’ll also find that you’re able to come up with better ideas, and your workflow is more efficient through the day (10, 11).
Exogenous ketones drinks are growing in popularity as a method to elevate blood ketone concentrations and mimic a ketogenic diet without the need for dietary changes (Ari et al., 2016; Cox et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017; Evans et al., 2017). The present study describes the pharmacokinetic and pharmacodynamics properties of ketone ester and salt drinks in humans at rest, and characterizes the effects of a prior meal, which is pertinent to use as a dietary supplement. The main findings were that KE drinks elevated blood d-βHB > 50% higher than KS drinks, the latter significantly increasing blood l-βHB, which was metabolized more slowly by the body. Both drinks had similar effects on FFA, TG, glucose and electrolyte concentrations, although with disparate effects on pH. A prior meal decreased total blood d-βHB appearance after a KE drink. Finally, either three KE drinks or nasogastric feeding effectively maintained nutritional ketosis over 1 mM for 9 h.
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.
There’s also the issue of supplement safety in general. All supplements—whether you’re talking about vitamins, minerals, herbs, or other nutritional mixes—are only loosely regulated. “We know that there is contamination of supplements here in the U.S., often from products that are manufactured abroad,” Palumbo says. In that case, “the same concerns apply to this as for any other supplement.”
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Increased levels of BHB in the body were found to be associated with greater cognitive performance through better performance in memory recall tests12 on a study of 20 subjects with Alzheimer’s disease or demonstration of a mild cognitive deficit. Similarly, BHB ketone esters helped to reverse symptoms of Alzheimer's Disease in one clinical case study.13 More research in humans is needed, but the various hypotheses are backed up by strong animal data.
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