Interestingly, the effects of exogenous ketones on blood substrate concentrations were preserved with the metabolic stimulus of a mixed meal. Following KE drinks, FFA and glucose fell and remained low in both fed and fasted subjects, despite higher insulin throughout the fed arm, suggesting that there was no synergistic effect of insulin and βHB to further lower blood glucose or FFA. In agreement with previous work, the threshold for the effects of βHB on glucose and lipids appears to be low (<1 mM), as there was no significant dose-response relationship between increasing blood βHB and the small changes in plasma FFA, TG or glucose across all of the study drinks (Mikkelsen et al., 2015).
While exogenous ketones (EK) are a newer supplement, having entered the market for consumers in just the past few years, scientists have been synthesizing ketone bodies in a lab since the 1960’s. They were useful for scientists studying their use for specific disease conditions, most notably childhood seizure disorders, though they were prohibitively expensive for consumers (1, 2).
I don’t recommend that you go straight for a 1-2 day fast, but begin by restricting yourself to certain eating windows. Typically people restrict themselves to the hours of 5pm – 11pm. People often refer to their fasting windows by numbers: 19/5 or 21/3, for example, means 19 hours of fasting and 5 hours eating or 21 hours fasting and 3 hours eating, respectively.
Two ground-breaking studies have recently been published on the effects of intermittent fasting on males. One group of researchers studied the effects that 16 hours of intermittent fasting had on males that lift weights. They found that muscle mass stayed the same, fat mass decreased significantly, and the males who fasted for 16 hours a day burned more fat for fuel compared to the control group that only fasted for 12 hours.
It’s not clear that the Weir coefficients used to estimate EE are relevant for someone in ketosis, let alone someone ingesting exogenous BHB. (The Weir formula states that EE is approximated by 3.94 * VO2 + 1.11 * VCO2, where VO2 and VCO2 are measured in L/min; 3.94 and 1.11 are the Weir coefficients, and they are derived by tabulating the stoichiometry of lipid synthesis and oxidation of fat and glucose and calculating the amount of oxygen consumed and carbon dioxide generated.) While this doesn’t impact the main observation—less oxygen was consumed with higher ketones—it does impact the estimation of EE and substrate use.

I noticed for myself that it helps if I add some highly nutritional foods to my diet before I go into ketogenic diet. Adding minerals and vitamins will aid your body in this difficult process and on top of that if you have a deficiency of some sort you will be even more hungry and it will make your transition more difficult, so why make it harder on your self if you can just add some leafy greens to your diet.

I just read your comment and was wondering the same thing. I can see how exogenous ketones can be a great energy boost to people on the ketogenic diet, but I don’t see how they can speed fat loss. Keto OS claims you can eat higher carbs and still see the benefits of ketosis. I don’t see how that is possible. the whole point of weight loss through ketosis is the breaking down of your own fat to create energy. I don’t see how exogenous energy will increase natural fat breakdown. I wish I could get a straight answer to this from somebody.
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.

If the goal is to deplete glucose levels so that we can start producing ketone bodies, then forcibly exerting physical energy through exercise is a great way to go about it. Keeping it relatively low intensity to begin with and working out in the morning is recommended as this helps to keep down your cortisol (stress hormone) levels. This only applies at the beginning of your keto adaptation process, as intense workouts such as HIIT once already keto-adapted will be completely fine.

We designed a test for each of the chosen benefit claims and enlisted the help of four of our Diet Doctor teammates to try out the supplements and go through the testing. They were Jonatan and Giorgos from the video team, Emőke from the recipe team and Erik from the IT team. We had a mix of people who were naturally in endogenous ketosis during testing, and people who were not.

2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.
Effects of ketone supplementation on blood glucose. a, b Blood glucose levels at times 0, 0.5, 1, 4, 8, and 12 h (for 10 dose) post intragastric gavage for ketone supplements tested. a Ketone supplements BMS + MCT and MCT significantly reduced blood glucose levels compared to controls for the duration of the 4-week study. BMS significantly lowered blood glucose only at 8 h/week 1 and 12 h/week 3 (b) KE, maintained at 5 g/kg, significantly reduced blood glucose compared to controls from week 1–4. BD did not significantly affect blood glucose levels at any time point during the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
Pruvit v Perfect Keto: One of the more popular brands for BHB salts is Pruvit (Keto OS). Pruvit is a good brand, but they do use some additives. Also, Pruvit is an MLM company that has tons of people pushing their products as the best weight loss product in the world. And you have to use one of their representatives’ referral codes to buy it. Learn more about the two in this Pruvit vs Perfect Keto comparison article.
For example, the popular Raspberry Ketones supplement is far different than what we have been discussing in this article. Raspberry ketones are unrelated to the ketones that are produced in the body and are not the same as the ketone salts that have been covered above. There are some limited studies that indicate raspberry ketones may be helpful for weight loss, but they are inconsistent. Raspberry ketones are the molecules that give raspberries their scent and flavor, and in some cases, aren’t even derived from raspberries at all.

Ketone monoester and diester compounds may circumvent the problems associated with inorganic ion consumption in KS drinks. KE ingestion rapidly increased blood ketone concentrations to >5 mM in animals (Desrochers et al., 1995a,b; Clarke et al., 2012a) and the first oral, non-racemic KE for human consumption, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, raised blood βHB concentrations to 3–5 mM in healthy adults (Clarke et al., 2012b; Shivva et al., 2016) and athletes (Cox et al., 2016; Holdsworth et al., 2017; Vandoorne et al., 2017). However, the pharmacokinetics and pharmacodynamics of this KE with confounding factors, such as prandial state or multiple KE drinks, have not been characterized.

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.
Again, there are very interesting animal studies plus some single case reports and small uncontrolled trials of humans with neurodegenerative disease and cancer given ketogenic diets and/or exogenous ketones (Murray 2016, Poff 2015, Roberts 2017, Newport 2015, Cunnane 2016). In some cases where the patient does not have the cognitive resources to comply with a well-formulated ketogenic diet, or where target blood levels of BOHB that work in animals are hard to achieve in humans by diet alone, supplemental ketones may have an important role to play in the prevention, management, or reversal of these disease categories.
 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.
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.

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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