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?
BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells. With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.
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.
Ketogenic Diets and Physical Performance – Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis. (http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-1-2)
As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
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
Yes. Both producing BHB in your liver as well as supplementing with beta hydroxybutyrate very safe. As we mentioned before, levels of 0.5 – 3.0 mmol measured in a blood test are completely normal. Some people get stressed out when they hear the term “diabetic ketoacidosis” or DKA, which is an entirely different metabolic scenario where your BHB levels skyrocket to 15-25 mmol blood readings.
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.
Some common short-term effects that some people experience in the early stages of the process are excessive thirst, fatigue and keto constipation. These minor side-effects occur due to a sudden change to a persons diet, but as I said, once your body starts to adjust to the process, you will start to feel normal again, if not better than before you started. We understand that constipation isn't exactly fun, but it's a small price to pay to experience the long-term health benefits.
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).
It’s sometimes the case that a person has been attempting to transition to a state of ketosis, but in spite of their best efforts, they seem stuck in a kind of limbo where they’re eating hardly any carbs, but they don’t seem to be losing weight or experiencing the other benefits of the keto diet. But the science is the science, which means if you’re doing everything right you should be in ketosis. If you’re not, or you seem to be drifting in and out of a keto state, it’s not your body’s fault, it’s your diet.
If you have been reading the science behind the ketogenic diet, you know there can be a lot of benefits associated with choosing this way of eating. There is usually a transition period from when someone chooses to go on a ketogenic diet and implements the changes to their menu to when they actually get into ketosis and are able to produce and burn ketones for fuel.
Ketones naturally exist in the body, being created during the process of fat metabolism and are therefore safe to consume even during pregnancy or breastfeeding. Supplements such as Ketologie’s PROBHB are simply providing ketones from an external (exogenous means literally ‘outside of the body’) source. However, if you suffer from any medical conditions and/or are on medications, it is always advisable to consult your health care provider prior to starting any new nutritional or dietary supplement.
Second, take a look back at table 2. Kegenix Prime scored as the “winning brand” for 4 out of the 7 markers tested: mental performance, satiety, mental clarity and energy. Compared to the other supplements, it also scored highest for physical performance, although none of the supplements were listed as a “winner” since the placebo outperformed them all for that marker.
The blood levels of BOHB that can be achieved with the salts or ester formulations are in the 1-3 mM range, similar to what can be achieved with a well-formulated ketogenic diet in insulin sensitive humans, but well below levels achieved after a 4-7 days of total fasting (Owen 1969). In more insulin resistant humans, the ester formulation may deliver higher blood levels than a sustainable diet (as opposed to short term fasting). For example, in the Virta IUH Study of over 200 patients with type 2 diabetes, blood ketone mean levels were 0.6 mM at 10 weeks and 0.4 mM after 1 year.
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.
After a minimal amount of internet "research," I decided to try my first exogenous ketones. I have used the ketogenic diet off and on for at 15 years and my body is pretty efficient at fat adapting. (Usually by the end of 2 strict days, I am in ketosis, but not without symptoms and intense cravings.) I can consistently fast from carbs for 20 - 24 hours and do this consistently. However, around hour 20, my mind begins to negotiate that intermittent fasting is advantageous too and that I can afford to have some carbs once a day. Hence the yo-yo effect.
To enter ketosis, up to 80%of your daily calories should come from fat. To put this into a frame of reference, if you eat 2,000 calories a day, 1,600 of those calories should come from fat sources. This comes out to roughly 144-170 grams of fat. Both quantity and quality are equally important, so consume fats from high-quality sources, like omega-3 and omega-6 fatty acids.
Intermittent fasting is using the same reasoning – instead of using the fats we are eating to gain energy, we are using our stored fat. That being said, you might think it’s great – you can just fast and lose more weight. You have to take into account that later on, you will need to eat extra fat in order to hit your daily macros (the most important thing). If you’re overeating on fats here, you will store the excess.
After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4
They’ve got enough science behind them to suggest they do work very well indeed, but watch out for the online ads featuring the raspberry ketone fat burners. Their name is little more than a parlour trick because this is not related in any way to ketones, a ketogenic diet or nutritional ketosis. They are merely the natural substance that gives raspberries their sweet aroma and flavour. Just because they’re marketed at the must-have fat burner, doesn’t mean they work and are one of the most widely spread Internet scams. There aren’t any human studies to back up raspberries claims so exercise a handful of caution when choosing your ketone supplier. Make sure they’re reputable, can be held accountable and are Australian made to set yourself up to become leaner while increasing your stamina.
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.
And zero-carb, followed by fasting for two meals, and then followed up by a second zero-carb meal is almost always all you need to get into ketosis fast. By Sunday or Monday morning, after a second night of no carbs, you'll be in a deep enough ketosis that hunger will crash and your energy will surge to help you transition into your low-carb diet of choice.
Human's ability to produce and oxidize ketone bodies arguably evolved to enhance survival during starvation by providing an energy source for the brain and slowing the breakdown of carbohydrate and protein stores (Owen et al., 1967; Sato et al., 1995; Marshall, 2010). The brain is normally reliant on carbohydrate as a substrate, being less able to metabolize lipids, despite adipose tissue representing a far larger energy store than muscle and liver glycogen. Therefore, during starvation, lipids are used for hepatic ketogenesis and, via ketone bodies, lipids sustain the brain. Endogenous production of the ketone bodies, d-β-hydroxybutyrate (βHB) and acetoacetate (AcAc), increases slowly, driven by interactions between macronutrient availability (i.e., low glucose and high free fatty acids) and hormonal signaling (i.e., low insulin, high glucagon and cortisol). Produced continuously under physiological conditions, blood ketone concentrations increase during starvation (Cahill, 1970), when consuming a “ketogenic” (low carbohydrate, high-fat) diet (Gilbert et al., 2000) or following prolonged exercise (Koeslag et al., 1980).
KE was synthesized as previously described . BMS is a novel agent (sodium/potassium- βHB mineral salt) supplied as a 50 % solution containing approximately 375 mg/g of pure βHB and 125 mg/g of sodium/potassium. Both KE and BMS were developed and synthesized in collaboration with Savind Inc. Pharmaceutical grade MCT oil (~65 % caprylic triglyceride; 45 % capric triglyceride) was purchased from Now Foods (Bloomingdale, IL). BMS was formulated in a 1:1 ratio with MCT at the University of South Florida (USF), yielding a final mixture of 25 % water, 25 % pure βHB mineral salt and 50 % MCT. BD was purchased from Sigma-Aldrich (Prod # B84785, Milwaukee, WI).
This molecule is quite essential if you are using your own fat for fuel, or taking BHB as an exogenous ketone supplement to increase energy production — essentially to be in nutritional ketosis. If you’re not certain about what ketones are or what nutritional ketosis is, you should back up a little bit and read more about that on my company site, Perfect Keto.
Some think so because higher ketone levels imply increased fuel for the brain and heart (that prefer ketones), and increased protection against inflammation and oxidation. But are the health benefits coming from the ketones themselves, or are they coming from the state you have to put your body in to actually produce them? And if you're kicking yourself out of ketosis by ingesting ketones would you still get the same benefits?
Exogenous ketones are created in a lab to accelerate both physical and mental performance. These ketone drinks were actually used in pro cycling races back in 2015, trading at prices that would make using your kidney as a bartering tool seem like a cut price deal. Fortunately, they’ve now come down in cost and are used often in between meals as a way of blackmailing your body into getting into ketosis way faster.
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.
So long long does it take to get into ketosis? This transition could take anywhere from 48 hours to one week. The length in time will vary depending upon your activity level, lifestyle, body type and carbohydrate intake. There are several ways you can speed up this process, like intermittent fasting, drastically decreasing your carb intake and supplementation.
The other option – which is the superior option – is the breakdown of fat into a fuel that can be used by the brain. This is a beautiful solution, because even the leanest individual will have weeks and weeks’ worth of energy stored as body fat. The body breaks down this fat in the liver and converts it into ketone bodies. The brain can then utilise these ketones as a fuel source – forgoing the need for stored glucose or constant consumption of carbohydrates. These ketones can also be used to make ATP.
Too much cortisol tells the liver that you are in physical danger and need a lot of energy fast. The brain doesn’t understand the difference between physical danger and emotional stress. When emotionally stressed, the brain thinks you’re in a life-and-death situation, so the liver comes to your rescue and gives you the glucose you need to fight off your attacker.
There is a great deal of positive speculation that exogenous ketones can be beneficial for inflammation, cognitive enhancement, and even protection against certain types of cancer. There is mounting evidence that the ketogenic way of eating can help many people, and when used appropriately with realistic expectations, exogenous ketone supplementation can enhance these positive effects (25).
Also known as the carb flu, the keto flu is commonly experienced by people who are transitioning to a Ketogenic diet. “Keto flu” is not actually flu but mimics the experience of flu with very similar symptoms. It can happen when someone who has become accustomed to relying primarily on carbohydrates as fuel removes them from their diet. Whilst this is a necessary step towards adjusting from being a sugar-burner to a fat-burner, the sudden change can trigger some unpleasant symptoms, much like withdrawing from an addictive substance. Keto flu symptoms can include drowsiness, nausea, dizziness, achy muscles, mental fogginess and an irritable mood. The good news though, is that most of these experiences relate to dehydration and electrolyte depletion, and so are easily prevented or managed. Simply adding a ¼ - ½ teaspoon of a high quality sea salt or sodium/potassium powder to a glass of water works wonders; however you may still require a separate magnesium supplement; particularly if you are prone to muscle cramps or restless legs. Another popular way to manage your electrolytes is via a good quality bone broth powder. Finally, since BHB’s are normally delivered via a mineral salt base*, keto flu symptoms are easily prevented or reduced by using an exogenous ketone supplement powder.
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.
Nutritional ketosis induced with the KD has proven effective for the metabolic management of seizures and potentially other disorders [1–26]. Here we present evidence that chronic administration of ketone supplements can induce a state of nutritional ketosis without the need for dietary carbohydrate restriction and with little or no effect on lipid biomarkers. The notion that we can produce the therapeutic effects of the KD with exogenous ketone supplementation is supported by our previous study which demonstrated that acutely administered KE supplementation delays central nervous system (CNS) oxygen toxicity seizures without the need for dietary restriction . We propose that exogenous ketone supplementation could provide an alternative method of attaining the therapeutic benefits of nutritional ketosis, and as a means to further augment the therapeutic potential of the KD.
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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