Interestingly, poly-BOHB has recently been reported to have important roles in mammalian mitochondrial membranes, cell membrane calcium channels, and in exotic functions like protein folding (Dedkova 2014). It exists in a variety of chain lengths, ranging from short to very long. It is not clear if humans can digest and use poly-BOHB consumed in the diet, but in animals, poly-BOHB appears to have probiotic and bowel protective functions. This is a rapidly evolving topic that we will be watching closely.
To be in ketosis, you need to get very specific about the macronutrient ratios hanging off your fork. This means eating 75% fats, 20% protein and 5% carbohydrates. It’ll see you getting 5-10% of your total calories from carbohydrates, which is roughly 25-30g of carbs per day, and diligently keeping this below the 50g threshold creates the ketosis that burns stored fat. Unlike the no-limit-protein option on the table when going low carb, eating more than 0.67-0.81g of protein per pound of bodyweight can hoof you out of ketosis because too much of it can be converted into glucose, blunting the benefits of the ketones. On the plus side, you will have a high fat intake, making your energy levels more balanced so you can train at higher intensities.

Exogenously delivered ketone supplements significantly altered rat weight gain for the duration of the study (Fig. 6). However, rats did not lose weight and maintained a healthy range for their age. Rats have been shown to effectively balance their caloric intake to prevent weight loss/gain [97–99]. Due to the caloric density of the exogenous ketone supplements (Table 1) it is possible for the rats to eat less of the standard rodent chow and therefore less carbohydrates while maintaining their caloric intake. Food intake was not measured for this study. However, if there was a significant carbohydrate restriction there would be a signifcant change in basal blood ketone and blood glucose levels. As the hallmark to the KD, carbohydrate restriction increases blood ketone levels and reduces blood glucose levels. Neither an increase in basal blood ketone levels nor a decrease in basal blood glucose levels was observed in this study (Fig. 7). Additionally, if there were an overall blood glucose decrease due to a change in food intake, this would not explain the rapid reduction (within 30 min) in blood glucose correlated with an elevation of blood ketone levels after an intragastric bolus of ketone supplement (Figs. 2, ​,33 and ​and44).
With oral ketone supplementation, we observed a significant elevation in blood βHB without dietary restriction and with little change in lipid biomarkers (Fig. 1). Over the 4 week study, MCT-supplemented rats demonstrated decreased HDL compared to controls. No significant changes were observed in any of the triglycerides or lipoproteins (HDL, LDL) with any of the remaining exogenously applied ketone supplements. It should be noted that the rats used for this study had not yet reached full adult body size [79]. Their normal growth rate and maturation was likely responsible for the changes in triglyceride and lipoprotein levels observed in the control animals over the 4 week study (baseline data not shown, no significant differences) [80, 81]. Future studies are needed to investigate the effect of ketone supplementation on fully mature and aged animals. Overall, our study suggests that oral ketone supplementation has little effect on the triglyceride or lipoprotein profile after 4 weeks. However, it is currently unknown if ketone supplementation would affect lipid biomarkers after a longer duration of consumption. Further studies are needed to determine the effects of ketone supplements on blood triglyceride and lipoproteins after chronic administration and as a means to further enhance the hyperketonemia and improve the lipid profile of the clinically implemented (4:1) KD.

Too much cortisol tells the liver that you are in physical danger and need a lot of energy fast. The brain doesn’t understand the difference between physical danger and emotional stress. When emotionally stressed, the brain thinks you’re in a life-and-death situation, so the liver comes to your rescue and gives you the glucose you need to fight off your attacker.
BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells.[10] With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.
This research is a good reminder to discuss with your doctor before taking any supplements. Given the widespread use of calcium supplements, more research is required before any final conclusions can be drawn. Several ketone companies have tried to avoid the large sodium loads but instead relied on a bump in the calcium content from the BHB ketone salts, seemingly without consideration for the aforementioned results. Calcium BHB will likely absorb slower compared to sodium BHB due to digestion and absorption kinetics.  For those looking to optimize brain uptake of ketones, this probably isn’t the best strategy (as uptake is directly proportional to the levels in the blood).   Be cautious of supplements running from the sodium and chasing the calcium BHB instead, and make sure you factor that into your overall daily needs.
If you read about ketosis in magazine or heard about it in a podcast and wanted to jump on the bandwagon, then I think you should avoid it. Remember, it is a strict diet, and the potential health downsides may not be worth the upsides, unless you are working with a medical professional and or you are tracking your labs to see what’s going on with your health (thyroid).
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.

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:
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.
Elliot received his BS in Biochemistry from the University of Minnesota and has been a freelance writer specializing in nutritional and health sciences for the past 5 years. He is thoroughly passionate about exercise, nutrition, and dietary supplementation, especially how they play a role in human health, longevity, and performance. In his free time you can most likely find him lifting weights at the gym or out hiking through the mountains of Colorado. He will also host the upcoming BioKeto podcast. You can connect with him on Facebook (https://www.facebook.com/elliot.reimers) and Instagram (@eazy_ell)
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+.
Hi! My question is, how low must my current daily carb count be in order to benefit from taking your exogenous ketones? I am a 33 year old female, keeping total carbs at 100-125 grams per day. My priority is fat loss, and I do HIIT training 4-5 days a week. I’ll soon be adding in heavier strength training. I don’t function well eating less than 100 total carbs a day. Could this even benefit me? And if it will benefit me, would the befits outweigh the sodium content? I keep my sodium at 2,000 mg a day, as I’m trying to avoid water weight.
Proper sleep is important for hormone function and repair of the body. Not getting enough sleep is tough on the adrenals and blood sugar regulation. Try to get at least seven hours of sleep per night. If you struggle with quality sleep, create an environment that is conducive for rest. This could be keeping your room cooler, turning off all electronic devices one to two hours before bedtime or using a sleep mask.

If you are having a weight loss plateau and you’ve been at the same weight for 3 or more weeks, try changing something to get back to that stable weight loss rate, like a ketone supplement. It would be exciting to lose more than that each week, but our bodies don’t adjust to dramatic changes well, and a slower rate of loss leads to more of the weight staying off in the future.

Our bodies are produce three types of ketone bodies for fuel: beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. Each is used by the body differently. Acetone is the least abundant, produced in much smaller amounts, and is usually exhaled through the lungs rather than being used as fuel.3 Acetoacetate is part of the metabolic pathway whereby humans make and use ketones, but it tends to be found in the blood at lower levels than BHB.


“Consumption of KETO//OS before exercise can result in significant decreases in oxygen demand and increases in performance. We recommend 30 minutes before a workout. Note: Pre-workout use is recommended after building up to a full dose. The best way to maximize energy, appetite control and sustain energy is to take KETO//OS first thing in morning. To maximize benefits, build up to 1 serving 3 times daily – morning, afternoon and early evening. May be used with carbohydrate supplements if desired or by itself as a non-carb, highly efficient energy source.”
It is important to define what it means to be “in ketosis”. If being “in ketosis” means having ketones in your blood, then of course ketone supplements get you into ketosis. But that is different from being in an endogenous ketogenic, fat-burning state as a result of following a ketogenic diet. Getting this distinction right will go a long way towards stopping ketone salts companies from using misleading marketing about the issue. We need to reach a consensus about what being “in ketosis” means and then force companies to use that definition.

Satiety decreased in both cases, slightly less with the supplements than with the placebo: participants reported feeling less hungry after taking the supplements than after taking the placebo. However, we are doubtful whether this would be enough of a difference to impact food intake and therefore induce weight loss indirectly, compared to not taking a supplement at all. Especially since, as noted before, BHB switches off lipolysis.
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.
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.

When your body transitions from using energy from carbohydrates to ketones, there can be a lot of nasty and unwanted side effects. These include low energy, bloating, irritability, headaches and fatigue. This is because your body is “in between” burning carbs and burning ketones and hasn’t become efficient at burning ketones and producing them from your fat stores yet.
Some common short-term effects that some people experience in the early stages of the process are excessive thirst, fatigue and keto constipation. These minor side-effects occur due to a sudden change to a persons diet, but as I said, once your body starts to adjust to the process, you will start to feel normal again, if not better than before you started. We understand that constipation isn't exactly fun, but it's a small price to pay to experience the long-term health benefits. 
Beta-Hydroxybutyrate (BHB) is a ketone body produced by the liver, from fat, for energy when glucose isn’t available. It ultimately becomes the body and brain’s primary source of energy. Since the liver naturally produces BHB during ketosis, the process can take quite some time, often resulting in symptoms of fatigue, hunger (cravings for sugar, a faster energy source), and mental cloudiness. That’s why supplementing BHB on a keto diet can have a profound positive impact.

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