Another source of the D-BOHB isomer is an evolutionarily ancient energy source for micro-organisms. Poly-BOHB is a long chain of D-BOHB molecules strung end-to-end. It functions in many single-cell organisms as a concentrated energy source similar to glycogen in mammals, but whereas glycogen breakdown releases individual glucose molecules, poly-BOHB hydrolysis releases single D-BOHB molecules.
Are you ready for a very basic metabolism overview? Most modern humans break down carbohydrates into glucose and this then breaks down further and enters mitochondria to produce ATP, which is the energy system of your cells. In other words, you use carbs for energy. When you are on a ketogenic diet, you are breaking down fats into things called ketone bodies, and this is how you provide your body with energy, instead of via carbohydrates. So, you’re either using carbohydrates for fuel or fat for fuel. 
Increased calcium levels in the bloodstream may contribute to the hardening of arteries (atherosclerosis), which in turn can lead to a heart attack.  Calcium from supplements enters the bloodstream in one bolus, whereas we usually tend to get calcium from foods in small doses from the breakdown process. This might explain why calcium from food doesn’t create the same risk that is introduced by calcium supplements. At first glance, it seems to be the case that high calcium intake –at least from supplements–may not be ideal.
Long-Term Effects of a Ketogenic Diet in Obese Patients – The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/)

There are many different variations of intermittent fasting as well. Dr. Dom D’Agostino, the well-known ketogenic diet researcher, suggests doing a longer intermittent fast for 3 days, 3 times a year. This means not eating for 3 days, and eating normally until the next fast. Daily intermittent fasts are recommended as well. He says that it is ideal to have one to two meals after fasting for most of the day to reap the benefits of intermittent fasting every day.

Sure Leslie, the goal is to induce the burning of stored fat in your body. This process usually take a few days of strictly limiting carbohydrate intake. Supplementing with exogenous ketones is a way to shortcut the wait time, essentially “tricking” your body into ketosis. I imagine supplementing with too many could have negative effects on fat loss, but the research is not out supporting that claim yet.


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.
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.
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. 
The difference in peak blood d-βHB concentrations between matched amounts of βHB as ester or salts arose because the salt contained l-βHB, as the blood concentrations of d- plus l-βHB isoforms were similar for both compounds. It is unclear if kinetic parameters of KE and KS drinks would be similar if matched d-βHB were taken in the drinks. Unlike d-βHB, blood l-βHB remained elevated for at least 8 h following the drink, suggesting an overall lower rate of metabolism of l-βHB as urinary elimination of l-βHB was in proportion to plasma concentration. Despite similar concentrations of total βHB, breath acetone was ~50% lower following KS drinks compared to KE, suggesting fundamental differences in the metabolic fates of D- and L-βHB. These findings support both previous hypotheses (Veech and King, 2016) and experimental work in rats (Webber and Edmond, 1977), which suggested that the l-isoform was less readily oxidized than the d-isoform, and is processed via different pathways, perhaps in different cellular compartments. It seems that l-βHB is not a major oxidative fuel at rest, and may accumulate with repeated KS drinks. However, the putative signaling role of l-βHB in humans remains unclear. In rodent cardiomyocytes, l-βHB acts as a signal that modulates the metabolism of d-βHB and glucose, Tsai et al. (2006) although no differences in blood glucose were seen here. Furthermore, L-βHB can act as a cellular antioxidant, although to a lesser extent than D-βHB (Haces et al., 2008).
Skipping breakfast on a keto diet is a popular way to boost ketone levels. Despite the age-old myth that breakfast is the most important meal of the day, research shows that breakfast skipping is not only safe but beneficial. Skipping breakfast causes intermittent ketosis and also suppresses appetite [6]. Make sure your next meal of the day isn't too late in the evening as studies show that eating meals late at night causes weight gain and impairs fat metabolism [7].
A sound sleep is highly associated with the dark. Also, studies have proven that our body’s natural defense mechanisms against cancer cells get activated in the absence of light (that’s why sleeping is the best way to natural healing). So turn off all the lights, TV screen, lamps, and all other light emitting devices at least 30 minutes before going to sleep. With this trick, you are actually preparing yourself to fall asleep.
More tolerable than MCT oil: MCT oil has been known to cause gastrointestinal distress in users, especially when taken in higher amounts. Exogenous ketones in the form of ketone salts, in comparison, are well-tolerated. Thus they enable one to avoid adverse GI events while providing the body with similar types of benefits. Figure 2 shows Ketone esters can be effective at reducing appetite. A combination of MCT oil and exogenous ketones may aid weight loss and allow a lower loading of ketone supplements, without the GI distress seen with MCT oil.
The human studies aren’t quite there yet, but it seems likely that they’d help. A recent human case study found that ketone esters added to the regular diet improved Alzheimer’s symptoms. Animal studies indicate that adding exogenous ketones to a regular lab (read: not ketogenic) diet can reduce seizure activity and improve overall symptoms in epilepsy animal models, reverse early neuronal hyperactivity in Alzheimer’s animal models, and reduce anxiety in rats.
In a nutshell… WOW! The chart above shows each of the games/categories I played, showing my prior 5-day averages compared to the day I took the ketone esters. Compared to my baselines, my scores increased across the board, with the biggest improvements in spatial orientation (+32.2%), working memory (+23.7%), quantitative reasoning (21.5%), task switching (+14.9%), and information processing (+14.9%). Below are more detailed comparisons:
Great information. And apparently I have found out what my problem is. I got into Keto a few weeks ago. Transitioned into ketosis after a week, and then had to travel….while I followed a keto diet as best I could, (I took your powdered MCT Oil with me and it is great), but I did fall out of ketosis. Now it’s been 2 weeks and I can’t seem to get back into ketosis.

Ketones are an alternate energy or fuel source for brain and body that our bodies have naturally produced and used for millennia. Ketones have recently leapt to the forefront of health and wellness conversations worldwide as the scientific body of research that seeks to understand their numerous unique properties and profound systemic effects has begun to grow (see below).
Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.

The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat [27]. The macronutrient ratio of the KD induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) in the blood. Acetone, generated by decarboxylation of AcAc, has been shown to have anticonvulsant properties [28–32]. Ketone bodies are naturally elevated to serve as alternative metabolic substrates for extra-hepatic tissues during the prolonged reduction of glucose availability, suppression of insulin, and depletion of liver glycogen, such as occurs during starvation, fasting, vigorous exercise, calorie restriction, or the KD. Although the KD has clear therapeutic potential, several factors limit the efficacy and utility of this metabolic therapy for widespread clinical use. Patient compliance to the KD can be low due to the severe dietary restriction - the diet being generally perceived as unpalatable - and intolerance to high-fat ingestion. Maintaining ketosis can be difficult as consumption of even a small quantity of carbohydrates or excess protein can rapidly inhibit ketogenesis [33, 34]. Furthermore, enhanced ketone body production and tissue utilization by the tissues can take several weeks (keto-adaptation), and patients may experience mild hypoglycemic symptoms during this transitional period [35].
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
More tolerable than MCT oil: MCT oil has been known to cause gastrointestinal distress in users, especially when taken in higher amounts. Exogenous ketones in the form of ketone salts, in comparison, are well-tolerated. Thus they enable one to avoid adverse GI events while providing the body with similar types of benefits. Figure 2 shows Ketone esters can be effective at reducing appetite. A combination of MCT oil and exogenous ketones may aid weight loss and allow a lower loading of ketone supplements, without the GI distress seen with MCT oil.
I eat one meal a day during a one-hour window and fast 23 or more hours every day. I want to use your ketones to get back into ketosis faster after that meal. Will that work? I am confused, because say at the end of my hour eating window I drink your ketones, sure there are lots of ketones suddenly in my body but I also have a big meal in my stomach. My body has to digest and use that food energy, so how do exogenous ketones help me in that case?
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.
Ketōnd discloses everything right there on their label so you know EXACTLY what you are getting. I have tried numerous ketone supplements and I can tell you I was not surprised that Ketōnd gave me more energy, mental clarity and improved my training more than any other ketone supplement. But take a few minutes and look at the product comparisons. You will see that Ketōnd has more ketones per serving and comes in at a fraction of the cost of every other product out there.

In conclusion, drinks containing exogenous ketones, in either ester or salt form, can raise concentrations of blood βHB in humans, although elevation of l-βHB lasts longer after racemic KS consumption. Both KE and KS drinks mildly altered acid-base balance. Exogenous ketones lowered blood glucose and lipids without inhibiting endogenous insulin secretion. The KE delivered highly repeatable blood concentrations of d-βHB, although ketosis was decreased by a meal. Uptake and elimination of d-βHB were similar when several drinks were consumed in succession. The dietary KE could maintain ketosis using drinks taken regularly around a normal meal pattern, or using a continuous infusion via a nasogastric tube. Therefore, ketone drinks are a viable and practical alternative to dietary strategies to achieve ketosis.
I am confused on the diet part. I’ve tried ketogenic diets and have experienced great health benefits (I’m diatabetic), but it also helped with sleeping through the night, increased energy, appetite suppression, and balancing of hormones. However forcing myself to eat fat and eliminate God foods like fruit, and trying to keep ratios of fat to protein to carbs was really hard for me. Can supplementing with the exogenic Ketones while having a diet of Proteins, veggies, fruits, healthy fats (avacado, cocnut oil, etc) and some grains (brown rice), produce ketosis?
Serial drinks or a continuous NG infusion of KE effectively kept blood ketone concentrations >1 mM for 9 h (Figure ​(Figure6).6). With drinks every 3 h, blood d-βHB rose and then fell, but had not returned to baseline (~ 0.1 mM) when the next drink was consumed. There was no significant difference in d-βHB Cmax between drinks 2 and 3 (3.4 ± 0.2 mM vs. 3.8 ± 0.2 mM p = 0.3), as the rate of d-βHB appearance fell slightly with successive drinks (0.07 ± 0.01 mmol.min−1 and 0.06 ± 0.01 mmol.min−1 p = 0.6). d-βHB elimination was the same after each bolus (142 ± 37 mmol.min, 127 ± 45 mmol.min; and 122 ± 54 mmol.min). When KE was given via a nasogastric tube, the initial bolus raised blood d-βHB to 2.9 ± 0.5 mM after 1 h, thereafter continuous infusion maintained blood d-βHB between 2–3 mM. Total d-βHB appearance in the blood was identical for both methods of administration (Serial drinks AUC: 1,394 ± 64 mmol.min; NG infusion AUC: 1,305 ± 143 mmol.min. p = 0.6).
Intermittent fasting is using the same reasoning – instead of using the fats we are eating to gain energy, we are using our stored fat. That being said, you might think it’s great – you can just fast and lose more weight. You have to take into account that later on, you will need to eat extra fat in order to hit your daily macros (the most important thing). If you’re overeating on fats here, you will store the excess.
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]
To enter ketosis, up to 80%of your daily calories should come from fat. To put this into a frame of reference, if you eat 2,000 calories a day, 1,600 of those calories should come from fat sources. This comes out to roughly 144-170 grams of fat. Both quantity and quality are equally important, so consume fats from high-quality sources, like omega-3 and omega-6 fatty acids.

Despite the recent growth of the ketone salt market, there is very little published work analyzing the effects of these products on any biomarkers or performance measurements in humans. Several studies have been carried out in rats,6,7 with blood BHB levels being relatively low (<0.5 mM) post-consumption of salt drinks. In humans, ketone salts provided peak D-BHB levels of 1 mM, whereas the same amount of BHB in a ketone ester (BD-BHB) raised blood BHB to 2.8 mM.5


The fate of excess ketones: In the event someone has an excessive amount of ketones in the blood, the body (specifically the kidneys) will work as quickly as possible to filter out ketones via urine rather than converting them to adipose tissue.9 This is not to say that you can’t gain fat if you consume an exorbitant amount of exogenous ketones, but that they are less prone to be converted to fat than other nutrients.


Another effect of the ketone drinks was to lower blood glucose, free fatty acids, and triglyceride levels. This sounds great. Elevated levels of all those markers are harbingers of disease, particularly if they remain chronically elevated. But think about what this means. If free fatty acids go down, that means adipose tissue isn’t being liberated for burning.
There have been studies done on long term ketogenic diets. This 2004 paper inn Experimental & Clinical Cardiology titled ‘Long-term effects of a ketogenic diet in obese patients’ concluded that obese patients following a ketogenic diet for 24 ‘reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.’
The protocols carried out in these studies were approved by the the South West Frenchay NHS REC (15/SW/0244) (Study 1) and London Queen's Square REC (14/LO/0288) (Study 2 and 3). The studies were carried out in accordance with the recommendations of the Declaration of Helsinki, apart from pre-registration in a database. All subjects gave written informed consent in accordance with the Declaration of Helsinki.

So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.

I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
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).
The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that  ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.
All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.

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