Several studies have investigated the safety and efficacy of ketone supplements for disease states such as AD and Parkinson’s disease, and well as for parenteral nutrition [40, 48–50, 100–103]. Our research demonstrates that several forms of dietary ketone supplementation can effectively elevate blood ketone levels and achieve deleted: therapeutic nutritional ketosis without the need for dietary carbohydrate restriction. We also demonstrated that ketosis achieved with exogenous ketone supplementation can reduce blood glucose, and this is inversely associated with the blood ketone levels. Although preliminary results are encouraging, further studies are needed to determine if oral ketone supplementation can produce the same therapeutic benefits as the classic KD in the broad-spectrum of KD-responsive disease states . Additionally, further experiments need to be conducted to see if the exogenous ketone supplementation affects the same physiological features as the KD (i.e. ROS, inflammation, ATP production). Ketone supplementation could be used as an alternative method for inducing ketosis in patients uninterested in attempting the KD or those who have previously had difficulty implementing the KD because of palatability issues, gall bladder removal, liver abnormalities, or intolerance to fat. Additional experiments should be conducted to see if ketone supplementation could be used in conjunction with the KD to assist and ease the transition to nutrition ketosis and enhance the speed of keto-adaptation. In this study we have demonstrated the ability of several ketone supplements to elevate blood ketone levels, providing multiple options to induce therapeutic ketosis based on patient need. Though additional studies are needed to determine the therapeutic potential of ketone supplementation, many patients that previously were unable to benefit from the KD may now have an alternate method of achieving therapeutic ketosis. Ketone supplementation may also represent a means to further augment ketonemia in those responsive to therapeutic ketosis, especially in those individuals where maintaining low glucose is important.
Exogenous ketones are also for those just looking to try it out. It lets anyone be able to access ketones simply by consuming these exogenous forms of ketones. Technically, MCTs are not an exogenous ketone such as BHB salts. They’re not ketones. But they readily convert into ketones. So MCT oils and powders are a great source of endogenous ketones. The end result is similar, and thus this top 5 list includes MCT oil powders as well as BHB salts.
Intellectual property covering uses of dietary ketone and ketone ester supplementation is owned by BTG Ltd., the University of Oxford, the National Institute of Health and TΔS Ltd. Should royalties ever accrue from these patents, KC and PC, as inventors, will receive a share of the royalties under the terms prescribed by the University of Oxford. KC is a director of TΔS Ltd., a company spun out of the University of Oxford to develop and commercialize products based on the science of ketone bodies in human nutrition. At the time of data collection and manuscript preparation, BS was an employee of TΔS Ltd., funded by the Royal Commission for the Exhibition of 1851. SH is an employee of NTT DOCOMO, Inc. (Japan). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

A recent study, Ketone Bodies Mimic the Life Span Extending Properties of Caloric Restriction, showed the effects of exogenous ketones on longevity (ketone esters, specifically) and concluded that ketones should be labeled as an “anti-aging” compound (suggesting that the real reason caloric restriction has been shown to extend life span is actually due to resulting ketosis).

Though research involving ketone supplements is still in the early stages, it seems promising. One study published in February 2018 in Obesity suggests exogenous ketone esters lower hunger hormones and act as appetite suppressors. That can lead to weight loss because “if we don’t feel hungry, gosh, we probably aren’t going to eat like we were,” Griffin says.

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.


Participants consumed 13.2 mmol.kg−1 of βHB (6.6 mmol.kg−1 or 1,161 mg/kg of KE) over 9 h, either as 3 drinks of 4.4 mmol.kg−1 of βHB at 3 h intervals (n = 12), or as an initial bolus of 4.4 mmol.kg−1 of βHB given through a nasogastric tube, followed by an infusion of 1.1 mmol.kg.h−1, beginning 60 min after the initial bolus, for 8 h (n = 4). Two participants completed both conditions (total n = 14). In both conditions, the KE was diluted to 1.5 L using the same citrus water as used in Study 2.
Of course, there may be some people who choose to take these supplements because they genuinely do feel they benefit from them. This is of course your choice and this article in no way aims to shame or criticize anybody. However, I do think that, for most people, eating a low-carb diet based on real foods is a lot more likely to be associated with the benefits that the supplements claim to provide than the supplements themselves.
The main distraction which we have these days in our lives are the gadgets. Therefore, in order to fall asleep early, you need to make sure that you turn off your phones, tablets, computer, TV etc… at least 30 minutes before bedtime. This helps avoid insomnia as well as keep you away from the bright blue light which can interfere with your biorhythm.

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. 
Now I can make a full review on these Perfect Keto products. I purchased the Salted Chocolate first. When I got it, I was mixing it with room temperature coffee and outing it over ice and adding heavy whipping cream. I hated the taste but kept making it that ways bc it got me 5lbs lost in one week. One day I got lazy and just mixed it with water and added heavy cream and it was delicious!! I highly suggest just mixing with water, adding heavy cream and over ice. I've lost 10 lbs in 15 days.
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.
In addition, the body regulates ketone production via ketonuria (peeing out excess ketones) and ketone-induced insulin release, which shuts off hepatic ketogenesis (the liver making more ketones when you have enough).   The insulin from this process could be increasing glucose disposal which, when coupled with PDH activation, could drive glucose levels quite low.
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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.

Ketones are produced by the body as a indicator of the body starting to use fat for fuel. Your body then uses those ketones as brain fuel (mostly) , but if you were to have a carb meal it would kick your body out of ketosis (fat burning state) because the carbs are a more easily usable source of energy. So why would you want to add a outside source of energy such as ketones not naturally produced by the body its self? It would kick you out of the fat burning state just like the carbohydrate meal because your body rather spare it’s own energy source as much as possible and also since the outside source ketones are not naturally produce by the body your body does not go into fat burning state because it doesn’t have to go through the natural process to produce its own ketones meaning the body is in its fat burning state since ketones are a by product of fat being used as fuel. Your body has to go through the natural process by itself. Outside ketones are treated as a alternative fuel source so your body has no reason to use fat as its fuel source. Just like carbs. Don’t fall for the scam do your homework it’s science backed up by facts. https://www.t-nation.com/diet-fat-loss/avoid-this-ketogenic-rip-off
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.

Neuroprotection: As humans age, the brain becomes more susceptible to neurodegeneration and subsequent conditions such as Alzheimer’s and Parkinson’s disease. Exogenous ketone supplementation appears to ameliorate the typical decline in cognitive function that comes with aging. The likely mechanism for this neuroprotective property is that ketone bodies reduce the inflammation and hyperexcitability that is normally exhibited as glucose metabolism declines in the brain.18, 19


Ketones are naturally slightly acidic, so the combination of BHB with sodium acts as a bit of a buffer to this acidity. Ketones will also naturally act as a diuretic, so you lose salt, potassium calcium and magnesium, and it is generally encouraged to increase sodium intake with ketones. The addition of sodium to the product will replenish this salt loss.
Hi all…thanks for your articles and info. I am currently on a paleo diet, but want to lose more weight and bring it up a notch w/ ketogenic diet and be in ketosis. Not sure which product is best? Do you take the MCT oil and also a ketone powder. I know it may be difficult at first, but I am up for the challenge as we start the new year and would like to loose 40 lbs by May/June. Please advise as to what products are best so I can purchase. THANKS
And zero-carb, followed by fasting for two meals, and then followed up by a second zero-carb meal is almost always all you need to get into ketosis fast. By Sunday or Monday morning, after a second night of no carbs, you'll be in a deep enough ketosis that hunger will crash and your energy will surge to help you transition into your low-carb diet of choice.
Hi. Thanks for the informative article! I have fallen down the exogenous ketone rabbit hole for the last 2 days trying to figure everything out. I am currently on a nutritional ketonic diet but after 8 months, I am finding it difficult to stay on it 100%. I would like to remain on a low-carb diet, but also have a little more flexibility in my food choices. If you take the expense out of the equation, which product would you recommend for someone who wants to use ketosis as a method of weight loss? Thank you so much.
If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.
But there have also been studies done showing that the Inuit Eskimo’s do not actually reach a state of ketosis. This is due to numerous factors. One being that the diet the eskimo’s eat ‘would not be expected to cause ketosis, because the calculated anti-ketogenic effect of the large protein ingestion was somewhat more than enough to offset the ketogenic effect of fat plus protein.” 
Recent studies suggest that many of the benefits of the KD are due to the effects of ketone body metabolism. Interestingly, in studies on T2D patients, improved glycemic control, improved lipid markers, and retraction of insulin and other medications occurred before weight loss became significant. Both βHB and AcAc have been shown to decrease mitochondrial reactive oxygen species (ROS) production [36–39]. Veech et al. have summarized the potential therapeutic uses for ketone bodies [28, 40]. They have demonstrated that exogenous ketones favorably alter mitochondrial bioenergetics to reduce the mitochondrial NAD couple, oxidize the co-enzyme Q, and increase the ΔG’ (free enthalpy) of ATP hydrolysis [41]. Ketone bodies have been shown to increase the hydraulic efficiency of the heart by 28 %, simultaneously decreasing oxygen consumption while increasing ATP production [42]. Thus, elevated ketone bodies increase metabolic efficiency and as a consequence, reduce superoxide production and increase reduced glutathione [28]. Sullivan et al. demonstrated that mice fed a KD for 10–12 days showed increased hippocampal uncoupling proteins, indicative of decreased mitochondrial-produced ROS [43]. Bough et al. showed an increase of mitochondrial biogenesis in rats maintained on a KD for 4–6 weeks [44, 45]. Recently, Shimazu et al. reported that βHB is an exogenous and specific inhibitor of class I histone deacetylases (HDACs), which confers protection against oxidative stress [38]. Ketone bodies have also been shown to suppress inflammation by decreasing the inflammatory markers TNF-a, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46, 47]. Therefore, it is thought that ketone bodies themselves confer many of the benefits associated with the KD.
Nutritional ketosis induced with the KD has proven effective for the metabolic management of seizures and potentially other disorders [1–26]. Here we present evidence that chronic administration of ketone supplements can induce a state of nutritional ketosis without the need for dietary carbohydrate restriction and with little or no effect on lipid biomarkers. The notion that we can produce the therapeutic effects of the KD with exogenous ketone supplementation is supported by our previous study which demonstrated that acutely administered KE supplementation delays central nervous system (CNS) oxygen toxicity seizures without the need for dietary restriction [29]. We propose that exogenous ketone supplementation could provide an alternative method of attaining the therapeutic benefits of nutritional ketosis, and as a means to further augment the therapeutic potential of the KD.
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.
Keto-adaption is a complex set of metabolic processes in which the body shifts from using primarily glucose for energy to using largely ketones and fat for energy. Achieving ketosis doesn’t mean the body is maximizing the use of these ketones; it takes longer than a few days for the body to get used to burning fat and ketones as its predominant fuels.
Over four visits, participants (n = 15) consumed 1.6 and 3.2 mmol.kg−1 of βHB as KE (141 mg/kg and 282 mg/kg of R-3-hydroxybutyl-R-1,3-hydroxybutyrate) or as KS (KetoForce, KetoSports, USA) sodium and potassium βHB, containing 1.6–3.2 g of each cation), plus 6 g of sweetener containing 19 kCal (4 g of carbohydrate) (Symrise, Holzminden, Germany), diluted to 300 ml using water. Drink blinding was not possible due to unmaskable differences in taste (bitter vs. salty).
There’s also the issue of supplement safety in general. All supplements—whether you’re talking about vitamins, minerals, herbs, or other nutritional mixes—are only loosely regulated. “We know that there is contamination of supplements here in the U.S., often from products that are manufactured abroad,” Palumbo says. In that case, “the same concerns apply to this as for any other supplement.”
Participants consumed 13.2 mmol.kg−1 of βHB (6.6 mmol.kg−1 or 1,161 mg/kg of KE) over 9 h, either as 3 drinks of 4.4 mmol.kg−1 of βHB at 3 h intervals (n = 12), or as an initial bolus of 4.4 mmol.kg−1 of βHB given through a nasogastric tube, followed by an infusion of 1.1 mmol.kg.h−1, beginning 60 min after the initial bolus, for 8 h (n = 4). Two participants completed both conditions (total n = 14). In both conditions, the KE was diluted to 1.5 L using the same citrus water as used in Study 2.
Meanwhile Brinkworth, et al., in their 2009 paper "Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function" looked at the effects on ketogenic diet on cognitive function and mood. The study participants ate a ketogenic diet for a year and the researchers found that mood levels decreased when compared to a group eating a high carb/low fat diet. They go on to remark “there was no evidence that the dietary macronutrient composition of LC and LF diets affected cognitive functioning over the long term, as changes in cognitive function were similar for both diets”.
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.
In addition to the Weir coefficients being potentially off (which impacts EE), the RQ interpretation may be incorrect in the presence of endogenous or exogenous ketones. As a result, the estimation of fat and glucose oxidation may be off (though it’s directionally correct). That said, the current interpretation seems quite plausible—greater fat oxidation when I had to make my ketones; less when I got my ketones for “free.”

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