Ketone supplementation did not affect the size of the brain, lungs, kidneys or heart of rats. As previously mentioned, the rats were still growing during the experimental time frame; therefore, organ weights were normalized to body weight to determine if organ weight changed independently to growth. There could be several reasons why ketones influenced liver and spleen weight. The ratio of liver to body weight was significantly higher in the MCT supplemented animals (Fig. 5). MCTs are readily absorbed in the intestinal lumen and transported directly to the liver via hepatic portal circulation. When given a large bolus, such as in this study, the amount of MCTs in the liver will likely exceed the β-oxidation rate, causing the MCTs to be deposited in the liver as fat droplets [94]. The accumulated MCT droplets in the liver could explain the higher liver weight to body weight percentage observed with MCT supplemented rats. Future toxicology and histological studies will be needed to determine the cause of the observed hepatomegaly. It should be emphasized that the dose in this study is not optimized in humans. We speculate that an optimized human dose would be lower and may not cause hepatomegaly or potential fat accumulation. Nutritional ketosis achieved with the KD has been shown to decrease inflammatory markers such as TNF-α, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46], which may account for the observed decrease in spleen weight. As previously mentioned, Veech and colleagues demonstrated that exogenous supplementation of 5 mM βHB resulted in a 28 % increase in hydraulic work in the working perfused rat heart and a significant decrease in oxygen consumption [28, 41, 42]. Ketone bodies have been shown to increase cerebral blood flow and perfusion [95]. Also, ketone bodies have been shown to increase ATP synthesis and enhance the efficiency of ATP production [14, 28, 40]. It is possible that sustained ketosis results in enhanced cardiac efficiency and O2 consumption. Even though the size of the heart did not change for any of the ketone supplements, further analysis of tissues harvested from the ketone-supplemented rats will be needed to determine any morphological changes and to understand changes in organ size. It should be noted that the Harlan standard rodent chow 2018 is nutritionally complete and formulated with high-quality ingredients to optimize gestation, lactation, growth, and overall health of the animals. The same cannot be said for the standard American diet (SAD). Therefore, we plan to investigate the effects of ketone supplements administered with the SAD to determine if similar effects will be seen when the micronutrient deficiencies and macronutrient profile mimics what most Americans consume.

Exogenous ketones can lower appetite during a fast. After an overnight fast, normal weight human subjects either drank a ketone ester supplement or a calorie-matched glucose drink. Compared to the glucose drinkers, the ketone drinkers had lower insulin, lower ghrelin, greater satiety, and less hunger. This can be useful for people trying to extend their fast who don’t want to or can’t yet deal with the hunger. You’re still taking in energy, but the metabolic profile remains similar to that of a fasted person.


-       Take ketone supplements (therapeutic ketosis): A second option is to consume ketones in the form of a supplement. Supplements like Perfect Keto Ketone Salts that provide the exact same ketone bodies that are produced naturally in the body. And while supplements are not a complete replacement for the benefits of ketones produced through diet, they do lower the barrier by allowing anyone to start benefiting from therapeutic ketones.
I am a little confused. I can see how EK’s can help up the state of ketosis, but as far is weight loss is concerned, aren’t the ketones you produce naturally created by the breaking down of your own fat? If I supplement with exogenous ketones, will that slow the natural creation of ketones? Especially if I am eating a higher amount of carbs. Would exogenous ketones speed fat loss, or slow it?
Second, there are inherent metabolic differences between boosting ketones via diet and boosting ketones via supplements. On a ketogenic diet, ketones go up because you’re converting body and dietary fat into ketone bodies. A rise in endogenous ketones means you’re burning fat and building the requisite machinery to metabolize the new energy source. On exogenous ketones, ketones go up because you ate some ketones; conversion of body and dietary fat into ketone bodies goes down if anything.

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.


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.
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There is also evidence that individuals who adhere to a low-carbohydrate or ketogenic diet may require higher sodium intakes. Due to their low carbohydrate contents, these diets reduce insulin levels. Since one of insulin’s roles is to decrease the excretion of sodium in the urine[7], low-carbohydrate and ketogenic dieters excrete more sodium than normal, and are encouraged to salt their meals to increase their sodium intake.
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.
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.
Great question. So if you are already in nutritional ketosis from your diet, exogenous ketones would still help raise ketone (energy) levels when you want that (maybe for focus at work or energy at the gym. They also help get you back into ketosis after cheat meals and skip the “keto flu” which is the period when your body is using up stored glycogen.

Once you hit the bed, the adrenal glands will be off and the body will enter the anabolic stage. This will allow your body to repair itself. If you stay up late for long periods of time your body will enter the hypercatabolic state. In this state, the levels of cortisol in your body increase significantly. This also increases the insulin resistance of the body which would again increase the blood sugar levels.


Should We Use Exogenous Ketones? Ketosis serves a purpose, and it’s probably why we’re able to survive on this planet. Being able to go without eating and use stored fats for energy is a survival tool and possibly far more as we’re now seeing with the keto diet. But it’s probably not a good idea to constantly take exogenous ketones and eat a high carb diet (high blood glucose levels). It’s not natural for the body to have high blood glucose and use ketones. This is a personal opinion, so 
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.
Athletic performance benefits: The use of exogenous ketone supplements for bettering physical/athletic performance is promising for several reasons. Firstly, taking exogenous ketones (particularly BHB salts) induces acute nutritional ketosis for upwards of eight hours, mimicking fasting physiology (e.g. increases fat burning, insulin sensitivity, etc.).[3]
A lot of people who use ketogenic diets will include a regular (i.e. weekly) carb refeed meal. There are various reasons behind doing this. If you are doing a lot of glycolic based training, then the carb refeed can help bump up muscle glycogen levels and in turn boost performance. Others use these refeeds as a way to keep their thyroid health in check, and finally some people use these refeeds as a ‘cheat day’ – so that they can still enjoy the pleasures from carbohydrates!

Second, there are inherent metabolic differences between boosting ketones via diet and boosting ketones via supplements. On a ketogenic diet, ketones go up because you’re converting body and dietary fat into ketone bodies. A rise in endogenous ketones means you’re burning fat and building the requisite machinery to metabolize the new energy source. On exogenous ketones, ketones go up because you ate some ketones; conversion of body and dietary fat into ketone bodies goes down if anything.


Uncontrolled diabetics may face some risks in using exogenous ketones. This is because when the body is unable to produce insulin (type I diabetics and extreme type II diabetics), it is unable to get sugar or glucose into the cells.  Therefore, the body will start producing ketones.  If these individuals do not use an insulin injection, they can overtime build up unsafe levels of ketones (6).
Exogenous ketones have a wide range of benefits that can enhance your fat-burning lifestyle. I personally use them daily as a strategy to heighten my mental performance and give my workouts an extra boost. For these purposes, I have also found it logical to combine exogenous ketones with other known health and performance boosting agents such as branched-chain amino acids and medicinal mushrooms.
You may find a tiny amount here and there is ok (i.e., 2g of sugar with a meal full of fat may be ok).  But if you are starting out I would recommend cutting all sugar from your diet, and most importantly avoiding any sugar consumption on an empty stomach. For best results track your ketone levels before and after meals to see the impact the food has on your ketone levels.
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
I am a little confused. I can see how EK’s can help up the state of ketosis, but as far is weight loss is concerned, aren’t the ketones you produce naturally created by the breaking down of your own fat? If I supplement with exogenous ketones, will that slow the natural creation of ketones? Especially if I am eating a higher amount of carbs. Would exogenous ketones speed fat loss, or slow it?
So if your high-fat diet includes a high amount of roasted seeds or roasted nuts, nut butters, heated oils such as heated coconut oil or heated extra virgin olive oil, barbecued meats or meats cooked at very high temperatures, then your triglyceride count is going to go up. You should have triglycerides that are less than 150mg/dL, and a triglyceride to HDL ratio that is no more than 4:1, and in most of the healthiest people I’ve worked with, triglycerides are under 100 and the triglyceride to HDL ratio is less than 2:1. If your ratio is whacked, your ketogenic diet isn’t doing you any favors.’
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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.
Because they’re so expensive, you want to make sure you pick a good one. Griffin and Langer say to ignore the companies that make these supplements sound too good to be true. Just like with any supplement, Griffin says it’s important to look at what’s in it. Beware of products with lots of fillers and instead go for one with a short, straightforward list of ingredients (Griffin likes the options from KetoSports).
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.
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).
If the claims about the benefits of exogenous ketones are accurate and true, then it’s fantastic news for people who are looking to enhance their keto lifestyle and who have the money to spend. But two of our core values are trustworthiness and goodness, and it is important to us to test assumptions made by marketing claims and help make sure that people are getting what they are told they are getting when they spend money on a product.
As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. Without exception, every time I ingested these compounds (which I’ve probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake. (At some point I will also write a post on Alzheimer’s disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)

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