Ketogenesis is the metabolism of fatty acids by β-oxidation. 4 This process gives acetyl CoA which then leads to β-hydroxy-β-methyglutaryl-CoA (HMG-CoA) as seen below5. HMG-CoA converts into Acetoacetone which can switch back and forth to BHB. Acetoacetone to Acetone conversion is irreversible (on the left below). Acetoacetate and BHB (via acetoacetate) are used to produce energy when converted back into acetyl-CoA within a cell’s mitochondria whilst Acetone is excreted in the breath and urine.4
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).
Obviously, cutting carbs is much easier than not eating anything at all for days on end. It's also safer for people with diabetes as it leads to a gradual decline in blood glucose . The carbs you have to reduce are known as net carbs. Those are the carbs that your body uses to make glucose. You calculate them by subtracting the grams of fiber from total carbs in a food item.
2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.
Dusty you assume only everyone wants fat burning. I think this is silly. The brain and heart will prefer ketones over carbohydrates when both are present in the blood stream. Look at the research and mechanism. I don’t want fat loss, I want better brain function. I also regularly eat carbs myself. This is one of the reasons I myself use exogenous ketones. No this isn’t a magic fat loss powder, but don’t sit here and quote T-nation trying to rebuttal this article acting like that is a credible source.
Again, there are very interesting animal studies plus some single case reports and small uncontrolled trials of humans with neurodegenerative disease and cancer given ketogenic diets and/or exogenous ketones (Murray 2016, Poff 2015, Roberts 2017, Newport 2015, Cunnane 2016). In some cases where the patient does not have the cognitive resources to comply with a well-formulated ketogenic diet, or where target blood levels of BOHB that work in animals are hard to achieve in humans by diet alone, supplemental ketones may have an important role to play in the prevention, management, or reversal of these disease categories.
When you start this process, changes in your daily food and drink intake are designed to increase the amount of healthy fats being burned by your liver, which produces and releases more of these endogenous ketones into your blood stream. When breastfeeding, the female body naturally burns more fat to produce the endogenous ketones, which is an infants resource to the nutrients they need for their young minds. As an adult, a lot of us have substituted the goodness of this compound for more sugar fueled energy. However, I'm sure there are many of you that are wondering right now, "does keto work at all and if so how long does ketosis last?" After numerous tests and studies, it has been recognized that it indeed does work and has been proven to have long lasting effects, so you can rest easy and maybe throw away those weight loss pills that claim instant results but don’t seem to do much.
Lots of good info but some things are just plain wrong. It takes 2 days max to get into ketosis if you stop eating carbs. Your body can only store roughly 2 days worth of glycogen. When those stores are exhausted your body will immediately turn to fat. It may take a week or several weeks to get “keto adapted” but it simply won’t ever take you more than 2 days to get into a state of ketosis.
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.
On day 29, rats were sacrificed via deep isoflurane anesthesia, exsanguination by cardiac puncture, and decapitation 4–8 h after intragastric gavage, which correlated to the time range where the most significantly elevated blood βHB levels were observed. Brain, lungs, liver, kidneys, spleen and heart were harvested, weighed (AWS-1000 1 kg portable digital scale (AWS, Charleston, SC)), and flash-frozen in liquid nitrogen or preserved in 4 % paraformaldehyde for future analysis.
I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
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)
If you stop eating carbs, your body first uses up glucose reserves stored in the liver and muscles. After it burns all that's left of glucose, it has no other options but to start burning fat. It can burn either your body's fat stores or the fat you eat. However, not all cells in your body can use fat to make energy and this is where ketones come into play.
For all studies, the area under the curve (AUC) of blood [βHB] was calculated using the trapezium rule. In Study 3, for each of the three drinks, the initial rate of d-βHB appearance was estimated using d-βHB concentrations at baseline and 30 min post-drink, and d-βHB elimination was estimated using the AUC between the post-drink peak (60 min) and trough (180 min) d-βHB concentrations, with a baseline correction to the value at 180 min.
The second ketone ester compound was developed at the University of South Florida. This is a diester of AcAc and BDO. In rodents, this ketone ester raises blood D-BHB to 1-4 mM and blood AcAc to up to 5 mM.19 There is one published study of this ketone ester in humans; results showed a 2% decrease in 31 km cycling time trial performance.16 This may be due to the high rate of side effects of this ester studied. Other factors may have been low levels of BHB (<2 mM), the short, high-intensity time trial used, or the use of AcAc vs. BHB.
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.
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).
An effective ketosis program requires that you control your appetite. Caffeine has been proven to be an excellent appetite suppressant. It can curb your appetite and reduce your cravings for food. If you are finding it hard to implement intermittent fasting, try to introduce coffee into the equation. If you are not into coffee drinks, try to take tea or use caffeine pills. Both of them contain caffeine, which can help you to adjust smoothly into fasting.
Follow our simple tips to get into ketosis and speed up the process. Our tips are scientifically-proven to work and are completely safe for everyone. If you need more guidance to achieve ketosis safely and effectively, enroll in our free Ketocademy course. The course will teach you everything there is to know about entering ketosis in less than 3 hours. Try it out today!
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!
The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.
I also chatted to some Prüvit reps, who told me that it might be necessary to keep taking the supplements for a couple of months to start to see more elevated ketones. Well, the proof is in the pudding (or in this case, in the fluorescent-coloured, artificial-tasting pink drink). But I would hesitate before spending money on a two-month supply just to find out if that’s true. Real Ketones’ Kegenix Prime was associated with a decrease blood ketones. Not a good start, and we’ll get back to this point later.
Personally, I do this on Friday night to Saturday night, so if something happens and my hunger hasn't crashed by Sunday morning, I have another day that I can go zero carb to keep the momentum going. While the body will trigger ketosis as soon as you run out of glycogen, hunger is attached to your triglyceride and insulin levels, which might take an extra day to normalize.
Funding. This work supported by an Industrial DPhil Fellowship to BS from the Royal Commission for the Exhibition of 1851. JM was supported by the EPSRC Doctoral Training Centre and Prize Fellowship; Ref: EP/M508111/1. The funding sources were not involved in the design, conduct or analysis of this study. TΔS Ltd. provided the ketone ester, ΔG®, and NTT DOCOMO Inc. provided the acetone meter for the study.
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.
For anyone who wants to get a bit more technical, research by Stubbs and colleagues shows that BHB shuts off lipolysis (fat breakdown). With endogenous ketosis there are many other factors that stimulate lipolysis meaning that a kind of balance is reached and lipolysis stays constant. But with exogenous ketosis those factors stimulating ketosis are not present, so the overall effect of the ingested BHB is to decrease lipolysis.
KE consumption decreased FFA from 0.6 to 0.2 mM, TG from 1.0 to 0.8 mM, and glucose from 5.5 to 4.7 mM by the end of the study (4 h). The effect was not altered by a meal (Figures 5A–C). Dextrose drinks also lowered FFA from 0.6 to 0.2 mM and TG from 1.0 to 0.7 mM (Figures 5A, B). This was likely mediated by the transient increase in glucose, which rose from 4.6 to 6.5 mM following the dextrose drink (Figure (Figure5C).5C). The anti-lypoytic effect of dextrose drinks was shorter than that of KE drinks as d-βHB concentrations were elevated for longer after KE drinks than glucose after dextrose drinks. Insulin increased to ~ 35 mU.ml−1 after both the meal and the dextrose drink, but also increased to 13 ± 2 mU.ml−1 when KE was consumed whilst fasted owing to the 15 g of glucose in the flavored drink used as a diluent (Figure (Figure5D5D).
I’m getting an increasing number of questions about exogenous ketones. Are they good? Do they work for performance? Is there a dose-response curve? If I’m fasting, can I consume them without “breaking” the fast? Am I in ketosis if my liver isn’t producing ketones, but my BOHB is 1.5 mmol/L after ingesting ketones? Can they “ramp-up” ketogenesis? Are they a “smart drug?” What happens if someone has high levels of both glucose and ketones? Are some products better than others? Salts vs esters? BHB vs AcAc? Can taking exogenous ketones reduce endogenous production on a ketogenic diet? What’s the difference between racemic mixtures, D-form, and L-form? What’s your experience with MCTs and C8?
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