Until there is more definitive information on the necessary blood levels and the differing proportions of BOHB an AcAc to optimize cellular and organ functions, it will be difficult to specify the dosing and duration of supplemental ketones. However for fuel use, and very likely for exercise performance as well, sustained blood levels of BOHB in the range of 0.5 mM to 1.0 mM are likely to be required. This is achieved physiologically by an estimated ketone production of 50-100 grams per day in a keto-adapted human.
Blood, urine, plasma, and breath ketone concentrations following mole-matched ketone ester or isocaloric dextrose drinks in fed and fasted subjects (n = 16) at rest. Data from both of the two study visits in each condition (fed and fasted) completed by an individual are included in the analysis. Values are means ± SEM. (A) Blood d-βHB. (B) AUC of blood d-βHB. (C) Urine d-βHB excretion. (D) Plasma acetoacetate (AcAc). (E) Measured breath acetone (ppm = parts per million). (F,G) Mean d-βHB Cmax and difference between βHB Cmax over two visits when subjects separately consumed two ketone ester drinks in both the fed (F) and fasted (G) state. X axis = mean d-βHB Cmax of the 2 visits (mM), Y axis = difference between d-βHB Cmax in each visit. 95% confidence limits are shown as dotted lines. Significance denoted by: *p < 0.05 fed vs. fasted.
It's a common misconception among those who are trying to lose weight that fat is dangerous, but this is not the case at all. You will need to rely on healthy sources of fat to reach ketosis, and this can be achieved by choosing the right type of food. Go with those that contain butter, olive oil, coconut oil and avocado oil, among others. Opt for oils that are not heavily processed so you can get the most benefits out of them.
To determine the reason for the differences in blood d-βHB concentration, the KE and KS drinks were analyzed for enantiomeric purity. The KE contained >99% of the d-isoform, whereas ~50% of the KS βHB was the l-isoform (Figure (Figure1D).1D). Plasma samples from participants who consumed the high dose KS drink (n = 5) were analyzed to reveal higher l-βHB than d-βHB, the total βHB Cmax being 3.4 ± 0.2 mM (Figure (Figure1E),1E), with a total βHB AUC of 549 ± 19 mmol.min. After 4 h, plasma l-βHB remained elevated at 1.9 ± 0.2 mM; differences in urinary excretion of the two isoforms could not explain this observation as both d- and l-βHB were excreted in proportion to their blood AUCs (Figure (Figure1F).1F). Therefore, in order to determine the time required for l-βHB elimination, a follow-up experiment was undertaken in which subjects (n = 5) consumed 3.2 mmol.kg−1 of βHB as KE and KS with hourly blood and breath sample collection up to 4 h, plus additional samples at 8 h and 24 h post-drink. l-βHB was found to be 1.1 ± 0.1 mM at 4 h, and 0.7 ± 0.2 mM after 8 h, but undetectable after 24 h (Figure 1G). Low amounts of d-βHB (0.3 ± 0.1 mM) were present at 24 h, presumably due to endogenous production. Both ketone drinks significantly increased breath acetone concentration, but at a slower rate than blood d-βHB, reaching a peak after 3 h that was twice as high following the KE (87 ± 9 ppm) than the KS (44 ± 10 ppm), suggesting that d-βHB was readily converted to acetone, but l-βHB was not (p < 0.005, Figure Figure1H1H).
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.
Exogenously delivered ketone supplements significantly altered rat weight gain for the duration of the study (Fig. 6). However, rats did not lose weight and maintained a healthy range for their age. Rats have been shown to effectively balance their caloric intake to prevent weight loss/gain [97–99]. Due to the caloric density of the exogenous ketone supplements (Table 1) it is possible for the rats to eat less of the standard rodent chow and therefore less carbohydrates while maintaining their caloric intake. Food intake was not measured for this study. However, if there was a significant carbohydrate restriction there would be a signifcant change in basal blood ketone and blood glucose levels. As the hallmark to the KD, carbohydrate restriction increases blood ketone levels and reduces blood glucose levels. Neither an increase in basal blood ketone levels nor a decrease in basal blood glucose levels was observed in this study (Fig. 7). Additionally, if there were an overall blood glucose decrease due to a change in food intake, this would not explain the rapid reduction (within 30 min) in blood glucose correlated with an elevation of blood ketone levels after an intragastric bolus of ketone supplement (Figs. 2, ,33 and and44).
Do I still follow a ketogenic diet? Not anymore. I was strict keto for 12 weeks – enough time to experiment and learn about it. I did enjoy parts (lots of fat!) but I don’t see it as a sustainable way of eating, nor did I benefit from it health or sports performance wise (more on this in an upcoming article). But, I was following a strict keto diet – sans carbs. I think if I were to follow a ketogenic diet AND incorporate a regular carb refeed then the results may be different.
Neuroprotective benefits: A natural part of the aging process is neurodegeneration, which is largely responsible for cognitive defects like Alzheimer’s disease. Recent research suggests that exogenous ketone supplementation can drastically slow neurodegeneration and the resulting decrease in mental function. However, the mechanism behind this finding remains to be elucidated; though, researchers suggest exogenous ketones act to reduce brain inflammation. Glucose, on the contrary, may actually accelerate inflammatory response in the brain.
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).
If you ever wondered how to get into ketosis, know that getting into ketosis is easy and completely natural for your body. All you need to do is follow the ketogenic diet which involves cutting down on carbs and eating lots of fat. You can also get into ketosis through fasting. But if your goal is weight-loss and reaping all the benefits of ketosis, the ketogenic diet is a must.
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
Great question. So if you are already in nutritional ketosis from your diet, exogenous ketones would still help raise ketone (energy) levels when you want that (maybe for focus at work or energy at the gym. They also help get you back into ketosis after cheat meals and skip the “keto flu” which is the period when your body is using up stored glycogen.
So I’ve been primarily on a Keto diet for almost 6 months. During this time, I have fine tuned a lot to get my ketone levels up (Eating more fat and less protein). Most recently, I have used blood measurements for my ketone levels and I fluctuate between .6 and 2.6. The higher readings I get on the days I workout in the morning (about 5 hours before I draw blood and take a reading). I don’t have any problems sticking to the diet. It only seems to get easier. I’ve also incorporated 16 hour fasts which also are becoming easier over time. My priority and motivation for doing a keto diet is first and foremost weight loss. So far I have lost 40 pounds and I need to lose about 20 more. I do however want to improve my performance (running) and strength (I am doing the Stronglifts 5×5 program now).
Humans in the hunter-gatherer era survived thanks to metabolic flexibility — the body’s ability to use different fuels for energy depending on the nutrients available. This adaptation was vital during a time when the source, quantity, and frequency of food was uncertain[*]. Most of the time, people were fasting, so their bodies ran on ketones, not glucose.
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