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.
Price: The supplements are expensive – very expensive. At the top end, if you follow Prüvit’s guidelines on “getting in the n8tive zone” (which is such a gimmicky marketing slogan it almost makes me cringe), you will require 2 servings of their Keto-OS product per day. This means around 60 servings per month, which will set you back a whopping $390 per month if you buy direct from their website! In the case of Prüvit, this is in part due to the multi-level marketing structure they operate under.
You see, when someone says ketosis is a natural state, they mean that ketosis is the body’s backup plan for those times when there isn’t any food to eat. It’s an evolutionary adaptation that developed over hundreds of thousands of years and springs from a time when our distant ancestors often had to go many days between decent meals. Fortunately, these days actual starvation is pretty rare so most people will never be in ketosis. But the physiological mechanism is still there, lurking in the background, readily accessible to anyone who is willing to trick their body into thinking it’s starving.

That said, there also remains the question of the relative benefits of AcAc versus BOHB, both as independent signaling molecules and as redox modulators in peripheral (aka non-hepatic) tissues. Seen from this perspective, AcAc generated in the liver acts as a NAD+ donor for the periphery, whereas pure BOHB taken orally, to the extent that it is retro-converted to AcAc (Sherwin 1975), potentially deprives the periphery of NAD+.
Weight loss benefits ushered the keto diet into the spotlight. That’s how most people have likely heard about ketones, a fuel source created naturally by the body when burning fat. But more and more research points to diverse applications of ketones in the blood outside of just fat loss, from improved endurance performance to the treatment of medical conditions like epilepsy.
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.
A common question is why BHB is the go-to ketone body for exogenous ketone supplements. The likely reason is a combination of its efficient conversion into energy and its ease of formulation. In other words, that it is easier to formulate BHB into a nutritional supplement. And the body efficiently converts BHB to acetoacetic acid, which effectively raises blood ketone levels.
But going keto takes work. You have to overhaul your diet, restrict certain classes of foods, and pay close attention to what you eat. People prefer to avoid work if they can. They like shortcuts. Exogenous ketone supplements promise a shortcut—swallow this pill or mix this powder into your water and see your ketones skyrocket without changing the rest of your diet.
My two cents: I wouldn’t take ketone supps if not on some sort of low(ish) carb diet because the idea of high levels of BOTH fuels (ie, ketones AND glucose) doesn’t seem physiologically appropriate… more like a recipe for disaster, and by “disaster,” I mean “out-of-control production of Reactive Oxygen Species” — this might not matter if you’re an athlete looking for a quick performance boost, because the fuels are going to be cleared rather quickly… not so much if you’re a desk jockey.
That’s exactly what ketones do: inhibit lipolysis, the breakdown of body fat into triglycerides and free fatty acids for burning. In normal conditions where ketones are produced endogenously, this is expected and beneficial. If homemade ketones increased lipolysis, you’d end up with ketoacidosis. You’d make ketones which released more body fat which got turned into more ketones which released more body fat which became more ketones. And on and on. It simply wouldn’t stop.
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.
The “BHB salt” is simply a compound that consists of sodium (Na+), potassium (K+), and the ketone body β-hydroxybutyrate. In supplements like Pruvit’s Keto OS these individual components are being held together by ionic bonds; however, when you consume the product, it is absorbed into the blood where it dissociates into free Na+, K+, and BHB since it is a water-based solution. Thus, consuming the product directly and immediately puts more ketones into your blood.
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.
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.

Increased levels of BHB in the body were found to be associated with greater cognitive performance through better performance in memory recall tests12 on a study of 20 subjects with Alzheimer’s disease or demonstration of a mild cognitive deficit. Similarly, BHB ketone esters helped to reverse symptoms of Alzheimer's Disease in one clinical case study.13 More research in humans is needed, but the various hypotheses are backed up by strong animal data.

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