Beta hydroxybutyrate floats around in your blood, and importantly, can cross different barriers to be able to be turned into energy at all times. One of the most important areas where this happens is in the brain. The blood-brain barrier (BBB) is usually a very tightly regulated interface that doesn’t allow the transfer of many molecules, but since BHB is such a rock star and so hydrophilic, your brain knows to let it in so it can bring energy to the party at any time. This is one of the main reasons why increased levels of ketosis lead to improved mental clarity, focus and reduction in neurodegenerative diseases.
We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
In conclusion, drinks containing exogenous ketones, in either ester or salt form, can raise concentrations of blood βHB in humans, although elevation of l-βHB lasts longer after racemic KS consumption. Both KE and KS drinks mildly altered acid-base balance. Exogenous ketones lowered blood glucose and lipids without inhibiting endogenous insulin secretion. The KE delivered highly repeatable blood concentrations of d-βHB, although ketosis was decreased by a meal. Uptake and elimination of d-βHB were similar when several drinks were consumed in succession. The dietary KE could maintain ketosis using drinks taken regularly around a normal meal pattern, or using a continuous infusion via a nasogastric tube. Therefore, ketone drinks are a viable and practical alternative to dietary strategies to achieve ketosis.
Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.
If you’re somebody who isn’t already a keto-goer, then you might be wondering why? Why do I need to limit my carbohydrate intake to get my body into a state of ketosis? Simply put, and without getting to technical; you want your body to be in a constant state where fat is the is the primary source of fuel for the body rather than glucose. You see, once you eat carbs, the body will break this down into glucose which it will then use for fuel before tapping into your fat reserves for energy. If you limit the amount of glucose that is in your system by restricting your carbohydrate intake, the body has no choice but to tap into your fat stores for energy. Fats are metabolised in the liver where ketones are then produced for your physical and cognitive needs.
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.
Hello! I’m planning on taking a short vacation and will be having “kept friendly” drinks, mostly vodka and water with lemon and stevia. When should I take my exogenous ketones? That night before bed or early the next morning or after the 3 day vacation is completely over? I’m unsure how to manage this to have the best odds of staying in ketosis and get back to burning FAT. Also, I just purchased Instaketones from Julian Bakery, what are your thoughts on this brand? Thanks for what you do!
Also, this experiement should be of interest. Two men followed a ‘traditional Eskimo’ diet for 1 year. After the year eating a low carb high fat diet, it was found that the men had a diminished tolerance to carbohydrates, something that did not occur in Eskimos eating the same diet. It took the mean nearly a month of eating a ‘normal diet’ before their glucose tolerance returned to baseline.
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!
The other potentially important distinction between nutritional ketosis and chemically-induced ketosis is the potential metabolic role played by liver AcAc production and redox status. Although the ratio of BOHB to AcAc in venous blood is typically 80% to 20%, classic studies by Cahill (1975) have observed important hepatic vein and peripheral arterio-venous gradients for this ratio in keto-adapted patients. What these observations imply is that the liver produces a higher proportion of AcAc than is found in the peripheral blood, and that this is due to uptake of AcAc in peripheral cells (principally muscle) with re-release as BOHB. In the process, the reduction of AcAc to BOHB produces NAD+, which is beneficial to mitochondrial redox state and mitochondrial function (Verdin 2015, Newman 2017).
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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