When the results for the supplement and the placebo were within 0.2 (either % or mmol/L) of each other, we classed the supplement as neither “better” nor “worse” than the placebo. We gave a “winning brand” sticker to the brand that scored highest against the placebo for each marker, but not for physical performance, since none of the supplements performed better than the placebo for that marker.
Unless otherwise stated, statistical analysis was conducted using Prism 6™ software. Values, expressed as means ± SEM, were considered significantly different at p < 0.05. Initial tests were undertaken to ensure that normality and sphericity assumptions were not violated. Subsequently, either one or two way repeated measures ANOVA, or Freidman's test with post-hoc Tukey or Dunnet's correction were performed, to compare changing concentrations of substrates, electrolytes, pH, insulin, breath and urinary βHB: both over time and between study interventions. In Study 2, data from each of the two study visits in each condition (fed and fasted) completed by an individual were included in the analysis.
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.
For the first part of my experiment, I would simply record my blood ketone and glucose levels over a period of two hours after taking the ketone esters. While I am already fairly keto-adapted and can attain nutritional ketosis fairly easily (> 0.5 mmol/L), it wasn’t until the end of my Five-day Fasting Mimicking Diet that I was even close to reaching therapeutic ketosis levels (>5.0 mmol/L).
The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.

Serial drinks or a continuous NG infusion of KE effectively kept blood ketone concentrations >1 mM for 9 h (Figure ​(Figure6).6). With drinks every 3 h, blood d-βHB rose and then fell, but had not returned to baseline (~ 0.1 mM) when the next drink was consumed. There was no significant difference in d-βHB Cmax between drinks 2 and 3 (3.4 ± 0.2 mM vs. 3.8 ± 0.2 mM p = 0.3), as the rate of d-βHB appearance fell slightly with successive drinks (0.07 ± 0.01 mmol.min−1 and 0.06 ± 0.01 mmol.min−1 p = 0.6). d-βHB elimination was the same after each bolus (142 ± 37 mmol.min, 127 ± 45 mmol.min; and 122 ± 54 mmol.min). When KE was given via a nasogastric tube, the initial bolus raised blood d-βHB to 2.9 ± 0.5 mM after 1 h, thereafter continuous infusion maintained blood d-βHB between 2–3 mM. Total d-βHB appearance in the blood was identical for both methods of administration (Serial drinks AUC: 1,394 ± 64 mmol.min; NG infusion AUC: 1,305 ± 143 mmol.min. p = 0.6).


Now that you have fasted for quite a long time, you can break your fast at around 4 to 5 pm. Try having some good fat for this purpose, such as coconut oil or MCT oil, butter, or any other healthy fat. MCT oil might come in as a better option in this case since it gets quickly absorbed by the body. It swiftly bypasses the gallbladder and reaches the liver where it is transformed to ketones rapidly.
In Study 2 a Student's unequal variance t-test with equal SD was used to compare urine βHB concentrations. Additionally, a linear mixed effects model was constructed to estimate partitions of variance in R, using the lme4 and blme packages (Chung et al., 2013; Bates et al., 2015). Feeding state and visit number were fixed effects in this model, and inter-participant variability was a random effect. Inter-participant variability was calculated according to the adjusted generalized R2 metric (as proposed by Nakagawa and Schielzeth, 2013), to partition variance between the fixed effects of feeding, inter-participant variability, and residual variability. The coefficient of variation for βHB Cmax and AUC were calculated using the method of Vangel (1996).
Selective attention involves focusing only on relevant information while suppressing the impulse to pay attention to irrelevant distractions. A v-shaped flock of birds are displayed. The center (target) bird points in one direction and is surrounded by birds that either match the target’s direction or do not. The task is to rapidly identify which direction the target bird is pointing.
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.

Increased calcium levels in the bloodstream may contribute to the hardening of arteries (atherosclerosis), which in turn can lead to a heart attack.  Calcium from supplements enters the bloodstream in one bolus, whereas we usually tend to get calcium from foods in small doses from the breakdown process. This might explain why calcium from food doesn’t create the same risk that is introduced by calcium supplements. At first glance, it seems to be the case that high calcium intake –at least from supplements–may not be ideal.


This is an excellent resource. Thank you for all the work and resources you found. i had never even heard of Adkins 72. I am keto but I always let Sunday be my high Carb cheat day.So im learning from this blog how to get back in ketosis in 24 hours after my 4pm meal on Sunday The Lords & family day. So im 25hr fasting. I would like to reference this article on my blog, thanks for helping me on my 100 lb lost journey.


The ‘carb-sparing’ effect from BHB suppresses the break down of muscle glycogen. This leads to lower lactate levels. When increasing exercise intensity, fat oxidation (burning) reaches a limit. At that point the muscle burns carbohydrates as fuel. But when consuming Ketone esters, the body does not make this switch. This suggests Ketones are being used instead. 11
Next, BHB salts are the only supplement that elevates BHB levels while muscle glycogen remains at capacity (low muscle glycogen can drastically impede long-duration athletic performance). In short, athletes who consume carb-based diets, and those on low-carb diets, stand to benefit from exogenous ketone supplements taken prior to training/exercise.
From my personal experience, there are plenty of ketogenic supplements that certainly do work, but you do have to be careful of the "phonies." You can find highly recommended ketones products that are endorsed by celebrity life coaches such as Timothy Ferris and Joe Rogan; then you also have those infomercial products that are probably as effective as eating Tic Tacs, which is why it is really important to do your research before experimenting. Once you are finished scouring this website full of its information, you should be well-equipped to make a calculated decision on whether this whole thing is for you and that means our mission is complete. 
For the ketone esters, on the other hand, repeated doses of 20-30 grams in any one day may be possible. Thus these products may be able to maintain a modest level of ketonemia without dietary carbohydrate restriction. Thus some of the cardiac and brain fueling benefits may follow, not to mention the epigenetic effects limiting oxidative stress and inflammation. But given the recent observation that administered ketone esters markedly reduce circulating free fatty acids (Myette-Cote 2018) — possibly due to an insulin-tropic effect or direct suppression of lipolysis (Taggart 2005) — their sustained use in people with underlying insulin resistance may compromise their long-term benefits by promoting weight gain unless combined with carbohydrate restriction.
Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.
Thank you, Mark! I am an ME/CFS patient, and I have improved quite a bit on a ketogenic diet, which I have been following for the past 3 months. I am slowly losing weight (much needed) and I wondered, does using exogenous ketones inhibit fat loss? I’m trying to balance the benefits of continuing weight loss with benefits in dealing with ME/CFS symptoms. Thank you for any info you can offer!

 “Though the small amount of carbohydrates in the diets may be more than balanced by the potential sugar production from the large amount of protein to keep the ratio of fatty acid to glucose below the generally accepted level of ketogenesis, the respiratory quotient data suggest another mechanism also” ß (most likely the CPT-1A mutation, which had not been discovered at that time)


I I started off interested in this product because it was cheaper than another popular Keto drink that I have known people to loose weight on. I have been drinking this about 2 weeks every morning on my way to work and I have never gotten the shakes jitters or felt a crash. I have also noticed my clothes to fit more comfortably as well. I do feel somewhat better taking this product I don’t know if it’s a mental thing but I will definitely purchase more and keep drinking it to hopefully see more difference
The effects of the two exogenous ketone drinks on acid-base balance and blood pH were disparate. In solution the ketone salt fully dissociates (giving a total of 3.2–6.4 g of inorganic cation per drink), allowing βHB− to act as a conjugate base, mildly raising blood and urine pH, as seen during salt IV infusions (Balasse and Ooms, 1968; Balasse, 1979). Urinary pH increased with the salts as the kidneys excreted the excess cations. In contrast, KE hydrolysis in the gut provides βHB− with butanediol, which subsequently underwent hepatic metabolism to form the complete keto-acid, thus briefly lowering blood pH to 7.31. Electrolyte shifts were similar for both KE and KS drinks and may have occurred due to βHB− metabolism, causing cellular potassium influx and sodium efflux (Palmer, 2015).
I carried out a survey among Diet Doctor users as background research to the experiment (a big thank you to the 638 people who responded!). In the survey, 28% of the respondents reported that they do take ketone supplements. The top four benefits that these respondents reported experiencing were increased energy, improved focus/cognition, reduced hunger and weight loss.
Exogenous ketones supplements is also necessary if you’re wondering how to get into ketosis in 24 hours. Directly ingesting ketones via salts or esters will boost blood ketone levels in the system. These are generally made up of beta-hydroxybutyrate (BHB) which is processed by the body to metabolise into ketones for energy. Some benefits of taking such supplements include anti-inflammatory properties, cancer prevention, increased cognitive function, weight-loss, and athletic performance enhancement.
When the results for the supplement and the placebo were within 0.2 (either % or mmol/L) of each other, we classed the supplement as neither “better” nor “worse” than the placebo. We gave a “winning brand” sticker to the brand that scored highest against the placebo for each marker, but not for physical performance, since none of the supplements performed better than the placebo for that marker.
KE was synthesized as previously described [29]. 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).
It's also a smart idea to start slowly with this supplement. We can thank Dave Asprey for the term “disaster pants” which has been used by those who try MCT oil at too high a dose when they first start using it. There is a chance that you can experience the same unpleasant gastrointestinal effect with exogenous ketones if you start with too high a dose, or if you maintain a higher carbohydrate diet while using this supplement. Used in appropriate doses, it gets absorbed through your stomach into your liver, then sent out to the rest of your body.
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.
However, it's important to NEVER overlook the power of exercise and of course sticking to a proper routine to get the most optimized results. The most common mistake people make is by treating any keto supplement like a "wonder drug" that will help them shred weight in their sleep. Seriously... how is that even scientifically possible. So if you are thinking about trying out a particular supplement, I would suggest two things:
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).

Exogenous ketones have a wide range of benefits that can enhance your fat-burning lifestyle. I personally use them daily as a strategy to heighten my mental performance and give my workouts an extra boost. For these purposes, I have also found it logical to combine exogenous ketones with other known health and performance boosting agents such as branched-chain amino acids and medicinal mushrooms.

All data are presented as the mean ± standard deviation (SD). Data analysis was performed using GraphPad PRISM™ version 6.0a and IBM SPSS Statistics 22.0. Results were considered significant when p < 0.05. Triglyceride and lipoprotein profile data were analyzed using One-Way ANOVA. Blood ketone and blood glucose were compared to control at the applicable time points using a Two-Way ANOVA. Correlation between blood βHB and glucose levels in ketone supplemented rats was compared to controls using ANCOVA analysis. Organ and body weights were analyzed using One-Way ANOVA. Basal blood ketone and blood glucose levels were analyzed using Two-Way ANOVA. All mean comparisons were carried out using Tukey’s multiple comparisons post-hoc test.
Ketosis supplements made in poor quality, have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men, and women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is really important to know what combination of compounds you are consuming, particularly while you are on this very strict diet because the wrong balance can really mess with you in the long term and won't give you the high performance that you are looking for. 

Eating around 20 grams of net carbs a day is as a foolproof way to get you into ketosis a quickly as is humanly possible. However, having 50 grams of total carbs will also get you into ketosis within three days [3]. This amount of carbs is enough to deplete glucose reserves. It's also low enough to prevent fat being used to make glucose and, instead, the body is forced to make ketones.


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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!
I feel like I should also mention that the GI discomfort is real, people. I would recommend starting this product on a weekend or a day where you’re able to just take it easy. After my first dose, which was only 1/2 scoop, I literally just felt like lying in bed all day due to feelings of nauseousness; however, by the next day I was fine and even bumped my dose to a full scoop.

We demonstrated that therapeutic ketosis could be induced without dietary (calorie or carbohydrate) restriction and that this acute elevation in blood ketones was significantly correlated with a reduction in blood glucose (Figs. 2, ​,33 and ​and4).4). The BMS ketone supplement did not significantly induce blood hyperketonemia or reduced glucose in the rats. The KE supplemented rats trended towards reduced glucose levels; however, the lower dose of this agent did not lower glucose significantly, as reported previously in acute response of mice [59]. MCTs have previously been shown to elicit a slight hypoglycemic effect by enhancing glucose utilization in both diabetic and non-diabetic patients [86–88]. Kashiwaya et al. demonstrated that both blood glucose and blood insulin decreased by approximately 50 % in rats fed a diet where 30 % of calories from starch were replaced with ketone esters for 14 days, suggesting that ketone supplementation increases insulin sensitivity or reduced hepatic glucose output [89]. This ketone-induced hypoglycemic effect has been previously reported in humans with IV infusions of ketone bodies [90, 91]. Recently, Mikkelsen et al. showed that a small increase in βHB concentration decreases glucose production by 14 % in post-absorptive health males [92]. However, this has not been previously reported with any of the oral exogenous ketone supplements we studied. Ketones are an efficient and sufficient energy substrate for the brain, and will therefore prevent side effects of hypoglycemia when blood levels are elevated and the patient is keto-adapted. This was most famously demonstrated by Owen et al. in 1967 wherein keto-adapted patients (starvation induced therapeutic ketosis) were given 20 IU of insulin. The blood glucose of fasted patients dropped to 1–2 mM, but they exhibited no hypoglycemic symptoms due to brain utilization of ketones for energy [93]. Therefore, ketones maintain brain metabolism and are neuroprotective during severe hypoglycemia. The rats in the MCT group had a correlation of blood ketone and glucose levels at week 4, whereas the combination of BMS + MCT produced a significant hypoglycemic correlation both at baseline and at week 4. No hypoglycemic symptoms were observed in the rats during this study. Insulin levels were not measured in this study; however, future ketone supplementation studies should measure the effects of exogenous ketones on insulin sensitivity with a glucose tolerance test. An increase in insulin sensitivity in combination with our observed hypoglycemic effect has potential therapy implications for glycemic control in T2D [40]. Furthermore, it should be noted that the KE metabolizes to both AcAc and βHB in 1:1 ratio [29]. The ketone monitor used in this study only measures βHB as levels of AcAc are more difficult to measure due to spontaneous decarboxylation to acetone; therefore, the total ketone levels (βHB + AcAc) measured were likely higher, specifically for the KE [14]. Interestingly, the 10 g/kg dose produced a delayed blood βHB peak for ketone supplements MCT and BMS + MCT. The higher dose of the ketogenic supplements elevated blood levels more substantially, and thus reached their maximum blood concentration later due to prolonged metabolic clearance. It must be noted that the dosage used in this study does not translate to human patients, since the metabolic physiology of rats is considerably higher. Future studies will be needed to determine optimal dosing for human patients.
Task switching is the process of adapting to changing circumstances (switching from one goal to another). Two cards are shown one above the other, and a combination of letter and a number (i.e., “A4”) will appear on one of the two cards. If it appears on top, the task is to indicate whether the number is an even number, and if on the bottom the task is to indicate whether the letter is a vowel.

In the second of these posts I discuss the Delta G implications of the body using ketones (specifically, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP generation, instead of glucose and free fatty acid (FFA). At the time I wrote that post I was particularly (read: personally) interested in the Delta G arbitrage. Stated simply, per unit of carbon, utilization of BHB offers more ATP for the same amount of oxygen consumption (as corollary, generation of the same amount of ATP requires less oxygen consumption, when compared to glucose or FFA).

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