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.
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.
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.
First, there’s something unnatural about having elevated levels of ketones and glucose together. It’s really hard to make that happen using traditional whole foods. The closest natural approximation you could get to it would be the traditional coconut-rich diets of the Kitava people in the South Pacific, where the medium chain triglycerides (MCT) in the coconut fat increased ketone production alongside the carbs in the fruit and tubers they ate. They had excellent metabolic health, but they weren’t anywhere close to a ketogenic diet. Coconut fat isn’t as ketogenic as purified MCT oil, let alone exogenous ketones.
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)

Many of us have heard the saying, “Don’t blame the butter for what the bread did.”  Similarly, don’t blame the sodium for what the fries did.  Sodium has been shown to help maintain fluid balance, normal muscle and nerve function, and blood pressure and volume[1]. The movement of sodium ions and other electrolytes across cell membranes helps to facilitate muscle contraction and nerve impulses. Electrolytes also help to maintain fluid balance across intracellular and extracellular spaces and blood volume.
Hi- Thank you for this super helpful post. I’m new to Keto and supplementing Keytones. I just got the Julian Bakery Keytones and am curious about how to take them as there are no instructions on the packaging. Indeed the website has a diet plan to follow with the keytones but I am very suspicious of it because it is 0 fat which I believe is not healthy for brain or body and given that I have soft tissue and joint issues, I try to eat enough fat daily. I want to lose weight and I crossfit 5 days per week. So how do I best start with using the keytone supplements? I took a scoop full yesterday when they arrived (in the early afternoon) but hadn’t yet eaten and I think that was a mistake because I had immediate diarrhea which lasted a few hours, even after eating.

Ketoacidosis is driven by a lack of insulin in the body.  Without insulin, blood sugar rises to high levels and stored fat streams from fat cells.  This excess amount of fat metabolism results in the production of abnormal quantities of ketones. The combination of high blood sugar and high ketone levels can upset the normal acid/base balance in the blood and become dangerous.  In order to reach a state of ketoacidosis, insulin levels must be so low that the regulation of blood sugar and fatty acid flow is impaired.


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.


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*:
Taking exogenous ketones not only eliminates the need to follow a strict ketogenic diet to achieve ketosis (so you can have your high carb cake and eat it too), it can also help users get there faster. “They can expedite the process of getting into ketosis and becoming fat adapted,” Davis explains. “They can also help people push past the keto flu and potentially experience more mental energy and clarity than from diet alone.”
All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.

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