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.
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.

After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4


There’s some support that exogenous ketones can be helpful for people already dutifully following the keto diet — but research has been limited. One thing we know for sure: These aren’t a get-thin-quick solution. “I think people are drawn to a quick, easy fix, kind of a magic bullet supplement, and it’s not that this won’t contribute to weight loss, but it’s not that magic bullet,” Griffin says.

If Prüvit’s Keto OS-Max is “not a weight loss supplement” as stated in their disclaimer, why is the official website full of success stories of people who claim to have lost huge amounts of weight from taking the supplements? Ketōnd also feature a number of weight loss success stories on their site. I will get to why there is a problem with weight loss claims later on.
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).

At day 29 of the study, animals were euthanized and brain, lungs, liver, kidneys, spleen and heart were harvested and weighed. Organ weights were normalized to body weight. Ketone supplementation did not significantly change brain, lung, kidney, or heart weights compared to controls (Fig. 5a, b, d, f). MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05) (Fig. 5c). Ketone supplements BMS + MCT, MCT and BD caused a significant reduction in spleen size (BMS + MCT p < 0.05, MCT p < 0.001, BD p < 0.05) (Fig. 5e). Rats administered KE gained significantly less weight over the entire study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls during weeks 2 – 4, and MCT animals gained less weight than controls at weeks 3 – 4 (Fig. 6). Increased gastric motility (increased bowel evacuation and changes to fecal consistency) was visually observed in rats supplemented with 10 g/kg MCT, most notably at the 8 and 12-h time points. All animals remained in healthy weight range for their age even though the rate of weight gain changed with ketone supplementation [53–54]. Food intake was not measured in this study. However, there was not a significant change in basal blood glucose or basal blood ketone levels over the 4 week study in any of the rats supplemented with ketones (Fig. 7).


Hi Acadia, just want to clear up a few things you noted in your post: The manufacture of BHB salts involves ionic bonding of an anion (beta-hydroxybutyrate) with a cation (Na+, K+, Ca+, Mg+). At least one of the exogenous ketone products you listed does in fact contain potassium ions. People taking potassium-sparing drugs need to know this and that raises concerns about leaving it off your chart. Some people are genuinely sodium sensitive even to small amounts of salt added to otherwise healthy foods. This can hold true even for those following ketogenic diets. The term you’re looking for… Read more »
Yes. Both producing BHB in your liver as well as supplementing with beta hydroxybutyrate very safe. As we mentioned before, levels of 0.5 – 3.0 mmol measured in a blood test are completely normal. Some people get stressed out when they hear the term “diabetic ketoacidosis” or DKA, which is an entirely different metabolic scenario where your BHB levels skyrocket to 15-25 mmol blood readings.
When choosing an exogenous ketone supplement, make sure to read the ingredients carefully. Brands that have a “proprietary blend” don’t allow you to see the quantities of each ingredient in their mix. You should know every detail about the supplements you choose, so you know exactly what is affecting your body, and you have control over the variables of your intake.
Lots of good info but some things are just plain wrong. It takes 2 days max to get into ketosis if you stop eating carbs. Your body can only store roughly 2 days worth of glycogen. When those stores are exhausted your body will immediately turn to fat. It may take a week or several weeks to get “keto adapted” but it simply won’t ever take you more than 2 days to get into a state of ketosis.

SHEER Ketones BHB Salts made this top 5 list because they do a good job of avoiding all the common unwanted additives and fillers in BHB salts. It’s good to see we have options to choose from when trying to avoid these types of ingredients. SHEER Ketones’ other ingredients include citric acid, fruit and vegetable juice powder for the color, and “natural flavors.” It uses a stevia leaf extract (Rebaudioside A).
Although several studies have linked calcium supplementation with an increased risk of heart attack and heart disease[18], other studies have not found the same association. For example, a study on calcium supplementation (1000 mg/day) in postmenopausal women indicated a reduced risk of hip fracture, but no increase in cardiovascular disease or mortality in the supplement group, compared to the placebo group[19]. Another study found no effect from calcium supplementation (600 or 1200 mg/day) on abdominal aortic calcification[20].
If you are trying to lose weight, following a ketogenic diet can help you burn fat fast. However, trying to get into ketosis can be a frustrating experience. Am I eating too many carbs, not enough fat, too much protein? Getting into ketosis usually takes 3 to 5 days at least, and can take people up to two weeks. Recently I have discovered a simple and easy way to get into ketosis very quickly. I went from eating lots of carbs one night, to in ketosis 24 hours later.
Although most of the research has been done utilizing ketone esters, ketone salt supplementation has the potential to provide additional benefits through the extra electrolytes/nutrients that are required to make the ketones. While ketone esters are expensive due to the manufacturing process involved in making them, ketone salts might be a more convenient option for both inducing a state of ketosis and elevating blood ketone levels for various reasons we will discuss in another article.
and by the way! the product you’re marketing has way too much salt – it will negate the true, natural process of any keto diet. salt will make you retain water, which is exactly what you don’t want to do, if you ever really want to lose weight! and if higher than normal blood pressure is your goal, enjoy responsibly! in fact, if you lower your overall salt intake, you will shed much more water weight in the first weeks, as mentioned elsewhere.. one of the secret cheats to get you going. drinking plenty of water and frequent urination will keep you properly hydrated – just be aware when testing with urine strips, too much water will give you a lower reading. stay hydrated, stay healthy – have fun losing the weight!
Animal procedures were performed in accordance with the University of South Florida Institutional Animal Care and Use Committee (IACUC) guidelines (Protocol #0006R). Juvenile male Sprague–Dawley rats (275–325 g, Harlan Laboratories) were randomly assigned to one of six study groups: control (water, n = 11), BD (n = 11), KE (n = 11), MCT (n = 10), BMS (n = 11), or BMS + MCT (n = 12). Caloric density of standard rodent chow and dose of ketone supplements are listed in Table 1. On days 1–14, rats received a 5 g/kg body weight dose of their respective treatments via intragastric gavage. Dosage was increased to 10 g/kg body weight for the second half of the study (days 15–28) for all groups except BD and KE to prevent excessive hyperketonemia (ketoacidosis). Each daily dose of BMS would equal ~1000–1500 mg of βHB, depending on the weight of the animal. Intragastric gavage was performed at the same time daily, and animals had ad libitum access to standard rodent chow 2018 (Harlan Teklad) for the duration of the study. The macronutrient ratio the standard rodent chow was 62.2, 23.8 and 14 % of carbohydrates, protein and fat respectively.

Anti-carcinogenic properties: Data seems to suggest that exogenous ketones are an effective anti-carcinogen. The reason behind this is that cancer cells are unable to use ketone bodies effectively, unlike most healthy tissues in the body. In fact, dietary ketone supplementation has been shown to increase survival rates of mice with systematic cancer by as much as 70%.17
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.
Lots of good info but some things are just plain wrong. It takes 2 days max to get into ketosis if you stop eating carbs. Your body can only store roughly 2 days worth of glycogen. When those stores are exhausted your body will immediately turn to fat. It may take a week or several weeks to get “keto adapted” but it simply won’t ever take you more than 2 days to get into a state of ketosis.

Follow our simple tips to get into ketosis and speed up the process. Our tips are scientifically-proven to work and are completely safe for everyone. If you need more guidance to achieve ketosis safely and effectively, enroll in our free Ketocademy course. The course will teach you everything there is to know about entering ketosis in less than 3 hours. Try it out today!
Consuming exogenous ketones isn't the same as following a ketogenic diet–the ketones in the blood haven't been naturally produced by the breakdown of fat stores. However, scientists believe many of the health benefits of the keto diet and fasting (aside from weight loss) are triggered by ketones. Therefore, raising ketone levels through either endogenous or exogenous ketosis could help to improve health and performance by:
When our cells undergo the process of autophagy, non-essential parts like damaged proteins are recycled and invading microorganisms and toxic compounds are removed. This means that autophagy plays an important role in stopping the aging process, reversing disease, and preventing cancer, but it doesn’t happen all the time. Fasting, protein restriction, and carbohydrate restriction are the three main ways that can initiate different autophagic processes — all of which are not the same. This is part of the reason why a ketogenic diet has so many positive effects, and it also shows you why intermittent fasting is a way to improve your diet even more.

BS, KC, and PC designed the research studies. BS, PC, RE, SM, and PS carried out the studies. SH provided the gas analyser used in the study on behalf of NTT DOCOMO Inc. BS, MS, and SM analyzed the data and performed statistical analysis in collaboration with JM. BS wrote the paper with help from KC, PC, and OF. KC had primary responsibility for final content. All authors read and approved the final manuscript.

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.


Halitosis (bad breath) – If you’re on a ketogenic diet you are probably aware that as the body starts to metabolize fat, ketones can cause poor breath. There is very little one can do about this, it’s just the nature of the beast. Unfortunately, this can also arise when using exogenous ketones, but it’s not as lasting as when on a ketogenic diet. Chewing gum or mints is about the best option if it becomes a noticeable issue. This maybe caused by over consumption of the ketone supplement, tailoring the quantity consumed may prevent excess BHB being converted to acetone, which is likely excreted by the lungs.

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+.
If you have already mastered the Very Low Carbohydrate (VLC) or ketogenic way of eating, and/or are eating at a caloric deficit, exercising or fasting you are naturally creating the optimal conditions for your body to produce ketones and put your body into nutritional ketosis. By strict adherence to a well-formulated ketogenic diet (complete with higher levels of mineral salts) you should be able to produce all the ketones you need naturally (endogenously). If you are new or inexperienced in ketogenic eating however; or if you or a family member struggles to adhere to a ketogenic diet, then supplementation with exogenous ketones may be very beneficial. Not only will ketone supplements help to mitigate hunger and carb cravings, but they will also help you stave off carb flu symptoms (see below), giving you the best possible chance of long-term success.
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